1. Information
    majorVersion:3 minorVersion:0 projectID:local projectVersionID:undef fileName:/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/8981359.csml convertedTime:2009.07.01.11:23

  2. Original Literature
  3. Model OverView
  4. Model Abstracts
  5. Model Detail
  6. Download
Original Literature Model OverView
Publication
Title CSF-1 and cell cycle control in macrophages.
Authors Hamilton JA.
Affiliation University of Melbourne, Department of Medicine, Royal Melbourne Hospital,Parkville, Victoria, Australia.
Abstract Control of cell proliferation involves a finely interwoven network of positiveand negative cell cycle regulators. Signal transduction pathways linking c-fms(CSF-1R) to cellular proliferation and differentiation are being explored. Partof the strategy is to use a series of G1 inhibitors to help pinpoint relevanttargets. Several inhibitors-8Br-cAMP, interferon gamma (IFN gamma), INFalpha/beta, lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF alpha),and dimethylamiloride-suppress CSF-1-stimulated proliferation in murine bonemarrow-derived macrophages (BMM) even when added in the mid- to late-G1 phase ofthe cell cycle. The down-modulating effects of the inhibitors on the expressionof the following cell cycle regulators have been examined: c-myc, cyclin D1 andD2, cdk4, Rb phosphorylation, E2F binding activity, ribonucleotide reductasesubunits, and PCNA. Some differences in the negative control of such regulatorswere found, for example, in the manner in which IFN gamma and cAMP down-regulatec-myc expression. Using blocking antibodies and BMM from type I IFN receptorknockout mice, it appears that one of these inhibitors, IFN alpha/beta, acts asan endogenous inhibitor in CSF-1-treated BMM and is also responsible, at leastin part, for the inhibition of cell cycle progression by LPS and TNF alpha.Another strategy has been to attempt to relate early biochemical changes inducedby CSF-1 to later changes in the G1 phase, partly by studying cycling versusnoncycling macrophages and partly by using cells expressing c-fms with tyrosinemutations in the intracytoplasmic region. CSF-1-mediated effects on thefollowing signal transduction molecules in these systems will be described:PI3-kinase, myelin basic protein kinases, Erks, and STAT transcription factors.
PMID 8981359
Model Abstract

Entity

G010205:DHFR G010228:IFN-beta G010239:c-myc G010373:tPA MO000000100:M-CSF MO000000148:Tyk2 MO000000289:TNF-alpha MO000007995:M-CSF-1-R MO000013119:STAT1 MO000013122:STAT3 MO000016665:IFNgamma MO000016882:LPS MO000019394:TLR4 e1: e10: e11: IFN -alpha e12:IFNalpha receptor e13:IFNalpha:receptor e14:Type I IFN antibody e16:LPS:TLR4 e17:receptor e18:TNF-alpha:receptor e19:unknown compounds e2: e20:cAMP e21:8Br-cAMP e22:Rb e23:E2F e24:Rb:E2F e25:cdk e26:E2F-1:CDNA e27:Rb:E2F-1 e29:Rb{p}:E2F-1 e3: e30:Rb{p} e31:E2F-1 e32:mRNA e33:thymidine kinase e34:Tyk2{pY} e35:PI3-kinase e36:PI3-kinase{pY} e37:c-fms e38:c-fms{pY} e39:unidentified proteins e4: e40:unidentified{p} e41:PI-3kinase:c-fms:unidentified e42:s6kinase e43:rapamycin e44:wortmannin e45:STAT1{active} e46:STAT3{active} e47:JAK kinases e48:JAK {active} e49:STAT e5:M-CSF:M-CSF-1-R e50: e51: e52: e53: e54: e55: e56: e57: e58: e59: e6:DNA e60: e61: e62: e63:STAT{pY} e64:STAT:STAT e65:IFN responsive gene e66:STAT:IFNRG e68:IFN-alpha e69:IFN-beta e7:DMA e70:IFNbeta e71:IFNbeta:receptor e8:IFNgamma receptor e9:IFNgamma:receptor

Process

p1 p10 p12 p13 p15 p17 p18 p19 p2 p20 p21 p22 p23 p24 p25 p26 p3 p30 p31 p32 p33 p34 p35 p36 p37 p38 p39 p4 p40 p41 p42 p43 p44 p45 p46 p48 p5 p50 p6 p7 p8 p9
Model Detail
316.0, 576.0
32.0, 32.0

DHFR

--

G010205

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p25

--

true true true true

csml-variable:Double

m93195

10

false

infinite

0

unit false false false
TRANSFACG010205

--

Go back
706.0, 730.0
28.0, 28.0

IFN-beta

--

G010228

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

--

p45 p6 p50

true true true true

csml-variable:Double

m93217

10

false

infinite

0

unit false false false
TRANSFACG010228

--

Go back
367.0, 531.0
34.0, 34.0

c-myc

--

G010239

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p18 p26

--

true true true true

csml-variable:Double

m93227

10

false

infinite

0

unit false false false
TRANSFACG010239

--

Go back
490.0, 458.0
35.5, 35.5

tPA

--

G010373

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p2

--

true true true true

csml-variable:Double

m93348

10

false

infinite

0

unit false false false
TRANSFACG010373

--

Go back
1066.0, 454.0
27.0, 27.0

M-CSF

--

MO000000100

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p1

true true true true

csml-variable:Double

m89

10

false

infinite

0

unit false false false
InterProIPR008001
TRANSPATHMO000000100

--

Go back
848.0, 500.0
24.0, 24.0

Tyk2

--

MO000000148

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p40

true true true true

csml-variable:Double

m132

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000000148

--

Go back
743.0, 1275.0
26.0, 26.0

TNF-alpha

--

MO000000289

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p12

true true true true

csml-variable:Double

m230

10

false

infinite

0

unit false false false
InterProIPR003636
TRANSPATHMO000000289

--

Go back
963.0, 503.0
34.0, 34.0

M-CSF-1-R

--

MO000007995

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p1

true true true true

csml-variable:Double

m1031

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000007995

--

Go back
472.0, 924.0
32.0, 32.0

STAT1

--

MO000013119

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p36

true true true true

csml-variable:Double

m1357

10

false

infinite

0

unit false false false
InterProIPR008967
TRANSPATHMO000013119

--

Go back
675.0, 1095.0
34.0, 34.0

STAT3

--

MO000013122

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p37

true true true true

csml-variable:Double

m1360

10

false

infinite

0

unit false false false
InterProIPR008967
TRANSPATHMO000013122

--

Go back
445.0, 1273.0
30.5, 30.5

IFNgamma

--

MO000016665

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p8

true true true true

csml-variable:Double

m1639

10

false

infinite

0

unit false false false
InterProIPR002069
TRANSPATHMO000016665

--

Go back
602.0, 1270.0
28.5, 28.5

LPS

--

MO000016882

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p10

true true true true

csml-variable:Double

m155666

10

false

infinite

0

unit false false false
TRANSPATHMO000016882

--

Go back
701.0, 1185.0
29.0, 29.0

TLR4

--

MO000019394

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p10

true true true true

csml-variable:Double

m3961

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019394

--

Go back
166.75, 2.6662788299897535
849.7491284518796, 1233.8357345121303

--

e1

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane

--

--

--

true true true true

csml-variable:Double

m1

0

false

infinite

0

unit false true false

--

Go back
186.1919065176218, 56.0996020803922
796.4957099412718, 1120.4455015837095

--

e10

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytosol

--

--

--

true true true true

csml-variable:Double

m10

0

false

infinite

0

unit false true false

--

Go back
618.0, 794.0
52.83737024221453, 28.179930795847753

IFN -alpha

--

e11

cso30:c:mRNA

cso30:i:CC_Cytosol

--

--

p4 p17 p48

true true true true

csml-variable:Double

m11

0

false

infinite

0

unit false false false

--

Go back
969.5, 930.0
29.244288224956062, 44.99121265377857

IFNalpha receptor

--

e12

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p5

true true true true

csml-variable:Double

m12

0

false

infinite

0

unit false false false

--

Go back
968.5, 698.0
31.0, 60.0

IFNalpha:receptor

--

e13

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m13

0

false

infinite

0

unit false false false

--

Go back
1125.0, 923.0
22.923076923076923, 34.38461538461539

Type I IFN antibody

--

e14

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p3 p13

true true true true

csml-variable:Double

m14

0

false

infinite

0

unit false false false

--

Go back
616.5, 1179.0
22.001096250822183, 42.582766937075206

LPS:TLR4

--

e16

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m16

0

false

infinite

0

unit false false false

--

Go back
964.5, 1116.0
31.231985940246044, 48.04920913884007

receptor

--

e17

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p12

true true true true

csml-variable:Double

m17

0

false

infinite

0

unit false false false

--

Go back
815.5, 1175.0
25.39267704450778, 49.147116860337654

TNF-alpha:receptor

--

e18

cso30:c:Complex

cso30:i:CC_Extracellular

--

true true true true

csml-variable:Double

m18

0

false

infinite

0

unit false false false

--

Go back
1081.0, 1081.0
53.338940285954585, 30.225399495374266

unknown compounds

--

e19

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p7 p15

true true true true

csml-variable:Double

m19

0

false

infinite

0

unit false false false

--

Go back
166.75, 2.6662788299897535
849.7491284518796, 1233.8357345121303

--

e2

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m2

0

false

infinite

0

unit false true false

--

Go back
722.0, 933.0
52.30445752733389, 29.639192598822536

cAMP

--

e20

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

p15

--

true true true true

csml-variable:Double

m20

0

false

infinite

0

unit false false false

--

Go back
199.0, 1260.0
58.08242220353238, 32.913372582001685

8Br-cAMP

--

e21

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p9 p21

true true true true

csml-variable:Double

m21

0

false

infinite

0

unit false false false

--

Go back
310.0, 222.5
44.21815254578385, 27.267860736566714

Rb

--

e22

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p19 p20

true true true true

csml-variable:Double

m22

0

false

infinite

0

unit false false false

--

Go back
242.0, 118.5
36.8, 27.600000000000005

E2F

--

e23

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p19 p24 p25 p26

true true true true

csml-variable:Double

m23

0

false

infinite

0

unit false false false

--

Go back
321.5, 74.0
29.672721213131148, 36.33394434260956

Rb:E2F

--

e24

cso30:c:Complex

cso30:i:CC_Cytosol

--

p19

--

true true true true

csml-variable:Double

m24

0

false

infinite

0

unit false false false

--

Go back
399.5, 80.0
24.36385590662105, 39.508955524250354

cdk

--

e25

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p21

true true true true

csml-variable:Double

m25

0

false

infinite

0

unit false false false

--

Go back
390.0, 446.5
67.88377474929288, 19.23373617896631

E2F-1:CDNA

--

e26

cso30:c:Complex

cso30:i:CC_Nucleoplasm

--

--

p20

true true true true

csml-variable:Double

m26

0

false

infinite

0

unit false false false

--

Go back
451.5, 256.0
32.252957840359926, 39.493417763706056

Rb:E2F-1

--

e27

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m27

0

false

infinite

0

unit false false false

--

Go back
533.0, 104.0
38.90243902439025, 31.12195121951219

Rb{p}:E2F-1

--

e29

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m29

0

false

infinite

0

unit false false false

--

Go back
183.74498256903755, 19.66126139902733
815.7591633138054, 1199.8457693740554

--

e3

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m3

0

false

infinite

0

unit false true false

--

Go back
595.0, 166.0
34.634146341463385, 27.707317073170724

Rb{p}

--

e30

cso30:c:Protein

cso30:i:CC_Cytosol

--

p22

--

true true true true

csml-variable:Double

m30

0

false

infinite

0

unit false false false

--

Go back
689.0, 328.5
37.42000402495472, 23.07566914872208

E2F-1

--

e31

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m31

0

false

infinite

0

unit false false false

--

Go back
524.0, 419.0
47.128027681660896, 25.134948096885815

mRNA

--

e32

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p23 p43

--

true true true true

csml-variable:Double

m32

0

false

infinite

0

unit false false false

--

Go back
258.0, 630.0
51.69550173010381, 27.570934256055367

thymidine kinase

--

e33

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p24

--

true true true true

csml-variable:Double

m33

0

false

infinite

0

unit false false false

--

Go back
904.0, 820.0
24.0, 24.0

Tyk2{pY}

--

e34

cso30:c:Protein

cso30:i:CC_CellComponent

--

p40

--

true true true true

csml-variable:Double

m34

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000000148

--

Go back
639.0, 103.5
42.15335077480378, 25.994566311129

PI3-kinase

--

e35

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p30 p35

true true true true

csml-variable:Double

m35

0

false

infinite

0

unit false false false

--

Go back
664.0, 252.0
40.97560975609756, 32.780487804878035

PI3-kinase{pY}

--

e36

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m36

0

false

infinite

0

unit false false false

--

Go back
734.0, 293.0
20.235734331150606, 46.697848456501404

c-fms

--

e37

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p31

true true true true

csml-variable:Double

m37

0

false

infinite

0

unit false false false

--

Go back
862.0, 409.0
19.95603367633302, 46.052385406922355

c-fms{pY}

--

e38

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m38

0

false

infinite

0

unit false false false

--

Go back
879.5, 160.0
24.319178909237277, 39.43650633930369

unidentified proteins

--

e39

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p32

true true true true

csml-variable:Double

m39

0

false

infinite

0

unit false false false

--

Go back
215.18570032175725, 49.40248089484302
752.8777278083659, 1140.3633303824224

--

e4

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m4

0

false

infinite

0

unit false true false

--

Go back
773.5, 306.0
21.951298047896955, 35.59669953713021

unidentified{p}

--

e40

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m40

0

false

infinite

0

unit false false false

--

Go back
707.5, 77.0
32.59919251238761, 45.487245366122224

PI-3kinase:c-fms:unidentified

--

e41

cso30:c:Complex

cso30:i:CC_Cytosol

--

p33

--

true true true true

csml-variable:Double

m41

0

false

infinite

0

unit false false false

--

Go back
103.0, 823.5
34.400000000000006, 25.800000000000004

s6kinase

--

e42

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p34 p35

true true true true

csml-variable:Double

m42

0

false

infinite

0

unit false false false

--

Go back
89.0, 717.0
53.76787216148024, 30.46846089150547

rapamycin

--

e43

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p34 p35

true true true true

csml-variable:Double

m43

0

false

infinite

0

unit false false false

--

Go back
1062.0, 225.0
52.22876366694701, 29.596299411269975

wortmannin

--

e44

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p35

true true true true

csml-variable:Double

m44

0

false

infinite

0

unit false false false

--

Go back
484.0, 992.0
32.0, 32.0

STAT1{active}

--

e45

cso30:c:Protein

cso30:i:CC_CellComponent

--

p36

--

true true true true

csml-variable:Double

m45

10

false

infinite

0

unit false false false
InterProIPR008967
TRANSPATHMO000013119

--

Go back
767.0, 1071.0
34.0, 34.0

STAT3{active}

--

e46

cso30:c:Protein

cso30:i:CC_CellComponent

--

p37

--

true true true true

csml-variable:Double

m46

10

false

infinite

0

unit false false false
InterProIPR008967
TRANSPATHMO000013122

--

Go back
255.0, 839.5
41.34433487623262, 25.49567317367679

JAK kinases

--

e47

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p38 p39

true true true true

csml-variable:Double

m47

0

false

infinite

0

unit false false false

--

Go back
290.0, 1094.5
43.83175689273496, 27.029583417186558

JAK {active}

--

e48

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m48

0

false

infinite

0

unit false false false

--

Go back
455.0, 1113.5
34.73938418192796, 21.422620245522236

STAT

--

e49

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p41

true true true true

csml-variable:Double

m49

0

false

infinite

0

unit false false false

--

Go back
972.5, 594.0
31.0, 60.0

M-CSF:M-CSF-1-R

--

e5

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m5

0

false

infinite

0

unit false false false

--

Go back
234.0, 330.0
612.5005213704808, 555.4706776674572

--

e50

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelopeLumen

--

--

--

true true true true

csml-variable:Double

m50

0

false

infinite

0

unit false true false

--

Go back
300.15461869550796, 343.16384753337127
358.14741845499253, 538.3617245565498

--

e51

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearPore

--

--

--

true true true true

csml-variable:Double

m51

0

false

infinite

0

unit false true false

--

Go back
241.98417811842347, 337.41387968139315
596.5321651336342, 540.6429183046706

--

e52

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearInnerMembrane

--

--

--

true true true true

csml-variable:Double

m52

0

false

infinite

0

unit false true false

--

Go back
243.12477499248388, 338.5544765554537
594.250971385513, 538.3617245565498

--

e53

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearLumen

--

--

--

true true true true

csml-variable:Double

m53

0

false

infinite

0

unit false true false

--

Go back
234.0, 330.0
612.5005213704808, 555.4706776674572

--

e54

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearOuterMembrane

--

--

--

true true true true

csml-variable:Double

m54

0

false

infinite

0

unit false true false

--

Go back
234.0, 330.0
612.5005213704808, 555.4706776674572

--

e55

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleus

--

--

--

true true true true

csml-variable:Double

m55

0

false

infinite

0

unit false true false

--

Go back
243.12477499248388, 343.81594270395556
594.250971385513, 538.3617245565498

--

e56

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleoplasm

--

--

--

true true true true

csml-variable:Double

m56

0

false

infinite

0

unit false true false

--

Go back
681.1139746317099, 558.119374812097
38.26566718861772, 34.64049871811714

--

e57

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearBody

--

--

--

true true true true

csml-variable:Double

m57

0

false

infinite

0

unit false true false

--

Go back
580.741449714388, 717.8029371805656
108.35670303574605, 98.09133116920191

--

e58

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleolus

--

--

--

true true true true

csml-variable:Double

m58

0

false

infinite

0

unit false true false

--

Go back
234.0, 330.0
612.5005213704808, 555.4706776674572

--

e59

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelope

--

--

--

true true true true

csml-variable:Double

m59

0

false

infinite

0

unit false true false

--

Go back
458.0, 749.5
60.0, 13.0

DNA

--

e6

cso30:c:Dna

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m6

0

false

infinite

0

unit false false false

--

Go back
378.36292658380285, 576.8465792634227
19.396991536823826, 9.339292221433706

--

e60

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Chromatin

--

--

--

true true true true

csml-variable:Double

m60

0

false

infinite

0

unit false true false

--

Go back
377.71520613162113, 548.9945998196138
66.39134634861503, 119.50442342750713

--

e61

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearChromosome

--

--

--

true true true true

csml-variable:Double

m61

0

false

infinite

0

unit false true false

--

Go back
405.56718557543115, 626.7210540814076
10.363527234905751, 10.36352723490576

--

e62

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearCentromere

--

--

--

true true true true

csml-variable:Double

m62

0

false

infinite

0

unit false true false

--

Go back
532.0, 1104.0
40.853658536585364, 32.6829268292683

STAT{pY}

--

e63

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m63

0

false

infinite

0

unit false false false

--

Go back
608.5, 970.0
30.138143642726224, 36.90384935844027

STAT:STAT

--

e64

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m64

0

false

infinite

0

unit false false false

--

Go back
670.0, 425.5
60.0, 13.0

IFN responsive gene

--

e65

cso30:c:Dna

cso30:i:CC_Nucleoplasm

--

--

p44

true true true true

csml-variable:Double

m65

0

false

infinite

0

unit false false false

--

Go back
642.0, 459.5
60.0, 17.0

STAT:IFNRG

--

e66

cso30:c:Complex

cso30:i:CC_Nucleoplasm

--

true true true true

csml-variable:Double

m66

0

false

infinite

0

unit false false false

--

Go back
1139.0, 751.0
18.59401309635173, 42.90926099158091

IFN-alpha

--

e68

cso30:c:Protein

cso30:i:CC_Extracellular

--

true true true true

csml-variable:Double

m68

0

false

infinite

0

unit false false false

--

Go back
1136.0, 813.0
16.53882132834425, 38.16651075771749

IFN-beta

--

e69

cso30:c:Protein

cso30:i:CC_Extracellular

--

true true true true

csml-variable:Double

m69

0

false

infinite

0

unit false false false

--

Go back
322.0, 1265.0
51.623212783851976, 29.253153910849456

DMA

--

e7

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p7 p21

true true true true

csml-variable:Double

m7

0

false

infinite

0

unit false false false

--

Go back
967.5, 991.0
32.32864674868189, 49.73637961335676

IFNbeta

--

e70

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p46

true true true true

csml-variable:Double

m70

0

false

infinite

0

unit false false false

--

Go back
968.5, 784.0
30.75219683655536, 47.311072056239006

IFNbeta:receptor

--

e71

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m71

0

false

infinite

0

unit false false false

--

Go back
527.5, 1171.0
33.0597539543058, 50.86115992970123

IFNgamma receptor

--

e8

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p8

true true true true

csml-variable:Double

m8

0

false

infinite

0

unit false false false

--

Go back
414.5, 1173.0
27.737557553168166, 53.68559526419645

IFNgamma:receptor

--

e9

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

--

true true true true

csml-variable:Double

m9

0

false

infinite

0

unit false false false

--

Go back
1063.0, 555.0
25.0, 25.0

p1

p1

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c1 : 1
stoichiometry:c2 : 1
stoichiometry:c3 : 1

m89*m1031*0.1

nodelay

--

true

0

false

PMID: 8981359 This report will focus on our attempts to understand some of the signal transduction pathways that lead from the interaction of CSF-1 with its receptor to subsequent DNAsynthesis a few hours later.

Go back
674.0, 1278.0
27.0, 27.0

p10

p10

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c26 : 1
stoichiometry:c27 : 1
stoichiometry:c28 : 1

m155666*m3961*0.1

nodelay

--

true

0

false

PMID: 8981359 LPS binds its corresponding receptor

Go back
842.0, 1258.0
27.0, 27.0

p12

p12

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c31 : 1
stoichiometry:c32 : 1
stoichiometry:c33 : 1

m230*m17*0.1

nodelay

--

true

0

false

PMID: 8981359 TNF-alpha binds its corresponding receptor.

Go back
551.0, 791.0
25.0, 25.0

p7

p13

cso30:i:CE_DNAReplication

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c139 : 1
stoichiometry:c147 : 1
stoichiometry:c18 : 1
stoichiometry:c35 : 1

m14*0.1

nodelay

--

true

0

false

PMID: 8981359 The inhibitors that we have used include dimethylamiloride (DMA) (which inhibits the Na1/H1 antiporter), IFNg, lipopolysaccharide (LPS), tumor necrosis factor a (TNFa), and a number of compounds that raise intracellular cAMP levels. These agents, which apparently have nothing in common, all suppress macrophage DNA synthesis. We propose that LPS and TNFa inhibit DNA synthesis, at least in part, through their induction of endogenous type I IFN. This proposition is supported by the fact that an antibody to type I IFN could partially reverse their inhibitory effects on CBABMM.

Go back
718.0, 1002.0
27.0, 27.0

p15

p15

cso30:i:ME_CAMPConcentrationElevation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c36 : 1
stoichiometry:c39 : 1

m19*0.1

nodelay

--

true

0

false

PMID: 8981359 The inhibitors that we have used include dimethylamiloride (DMA) (which inhibits the Na1/H1 antiporter), IFNg, lipopolysaccharide (LPS), tumor necrosis factor a (TNFa), and a number of compounds that raise intracellular cAMP levels. These agents, which apparently have nothing in common, all suppress macrophage DNA synthesis.

Go back
834.0, 906.0
27.0, 27.0

p17

p17

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c42 : 1
stoichiometry:c44 : 1
stoichiometry:c140 : 1

m11*m18*0.1

nodelay

--

true

0

false

PMID: 8981359 We propose that LPS and TNFa inhibit DNA synthesis, at least in part, through their induction of endogenous type I IFN.

Go back
386.0, 598.0
27.0, 27.0

p18

p18

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c45 : 1
stoichiometry:c46 : 1
stoichiometry:c47 : 1

m5*0.1

nodelay

--

true

0

false

PMID: 8981359, 7761098 We have shown that IFNg can reduce the CSF-1? dependent c-myc mRNA expression.

Go back
319.0, 159.0
25.0, 25.0

p19

p19

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c50 : 1
stoichiometry:c51 : 1
stoichiometry:c52 : 1

m22*m23*0.1

nodelay

--

true

0

false

PMID: 8981359 Rb is a member of a family of tumor suppressor proteins that interact with transcription factors such as the E2F family.

Go back
753.0, 557.0
30.0, 30.0

p2

p2

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c4 : 1
stoichiometry:c5 : 1

m5*0.1

nodelay

--

true

0

false

PMID: 8981359, 6967488 CSF-1 increases plasminogen activator expression in murine macrophages (Hamilton et al., 1980).

Go back
318.0, 302.0
27.0, 27.0

p20

p20

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c53 : 1
stoichiometry:c54 : 1
stoichiometry:c55 : 1
stoichiometry:c29 : 1

m22*m26*0.1

nodelay

--

true

0

false

PMID: 8981359, 1534305 For example, it is believed that Rb sequesters E2F-1 from the DNA, thus inhibiting its transcriptional activity. When Rb is phosphorylated, it releases E2F-1 which is then able to activate the transcription of genes.

Go back
396.0, 192.0
23.0, 23.0

p21

p21

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c57 : 1
stoichiometry:c58 : 1
stoichiometry:c72 : 1
stoichiometry:c34 : 1
stoichiometry:c56 : 1
stoichiometry:c73 : 1
stoichiometry:c59 : 1

m25*m27*0.1

nodelay

--

true

0

false

PMID: 8981359 One of the known signal transduction systems that we have studied is the cyclin D/cdk system. This kinase system is believed to control retinoblastoma protein (Rb) phosphorylation. PMID: 8981359, 1534305 For example, it is believed that Rb sequesters E2F-1 from the DNA, thus inhibiting its transcriptional activity. When Rb is phosphorylated, it releases E2F-1 which is then able to activate the transcription of genes. PMID: 8981359 The addition of LPS, 8Br-cAMP, DMA, or IFNg resulted in suppression of the degree of Rb phosphorylation.

Go back
534.0, 206.0
27.0, 27.0

p22

p22

cso30:i:ME_Dissociation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c60 : 1
stoichiometry:c61 : 1
stoichiometry:c62 : 1

m29*0.1

nodelay

--

true

0

false

PMID: 8981359, 1534305 For example, it is believed that Rb sequesters E2F-1 from the DNA, thus inhibiting its transcriptional activity. When Rb is phosphorylated, it releases E2F-1 which is then able to activate the transcription of genes.

Go back
482.0, 374.0
27.0, 27.0

p23

p23

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c63 : 1
stoichiometry:c65 : 1
stoichiometry:c64 : 1

m31*0.1

nodelay

--

true

0

false

PMID: 8981359, 1534305 For example, it is believed that Rb sequesters E2F-1 from the DNA, thus inhibiting its transcriptional activity. When Rb is phosphorylated, it releases E2F-1 which is then able to activate the transcription of genes.

Go back
250.0, 554.0
27.0, 27.0

p24

p24

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c66 : 1
stoichiometry:c67 : 1

m23*0.1

nodelay

--

true

0

false

PMID: 8981359 Some of the genes that are believed to be controlled by the E2F family of transcription factors are important for cell cycle progression. including thymidine kinase, dihydrofolate reductase, and c-myc.

Go back
290.0, 494.0
27.0, 27.0

p24

p25

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c68 : 1
stoichiometry:c69 : 1

m23*0.1

nodelay

--

true

0

false

PMID: 8981359 Some of the genes that are believed to be controlled by the E2F family of transcription factors are important for cell cycle progression. including thymidine kinase, dihydrofolate reductase, and c-myc.

Go back
334.0, 466.0
27.0, 27.0

p24

p26

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c70 : 1
stoichiometry:c71 : 1

m23*0.1

nodelay

--

true

0

false

PMID: 8981359 Some of the genes that are believed to be controlled by the E2F family of transcription factors are important for cell cycle progression. including thymidine kinase, dihydrofolate reductase, and c-myc.

Go back
558.0, 702.0
27.0, 27.0

p3

p3

cso30:i:CE_DNAReplication

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c6 : 1
stoichiometry:c14 : 1
stoichiometry:c16 : 1
stoichiometry:c74 : 1
stoichiometry:c7 : 1

m5*m14*0.1

nodelay

--

true

0

false

PMID: 8981359 This report will focus on our attempts to understand some of the signal transduction pathways that lead from the interaction of CSF-1 with its receptor to subsequent DNAsynthesis a few hours later. These results suggested that in most CSF-1?treated BMM cultures, there was an induction of IFNa/b which could influence the results by suppressing the level of DNA synthesis measured. We confirmed that CSF-1 could also induce low levels of IFNa/b production, as a cell-associated activity, in CBA BMM cell cultures. When an antibody to type I IFN was included, there was a regular increase in the rate of DNA synthesis in response to CSF-1

Go back
755.0, 203.0
25.0, 25.0

p30

p30

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c87 : 1
stoichiometry:c88 : 1
stoichiometry:c89 : 1

m35*m5*0.1

nodelay

--

true

0

false

PMID: 8981359 The PI3-kinase was tyrosine phosphorylated soon after adding CSF-1 to the BMM.

Go back
763.0, 371.0
25.0, 25.0

p31

p31

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c90 : 1
stoichiometry:c91 : 1
stoichiometry:c92 : 1

m37*m5*0.1

nodelay

--

true

0

false

PMID: 8981359 c-fms was also immunoprecipitated and tyrosine phosphorylated, in addition to a number of proteins which we are now trying to identify.

Go back
859.0, 251.0
25.0, 25.0

p31

p32

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c93 : 1
stoichiometry:c94 : 1
stoichiometry:c95 : 1

m5*m39*0.1

nodelay

--

true

0

false

PMID: 8981359 c-fms was also immunoprecipitated and tyrosine phosphorylated, in addition to a number of proteins which we are now trying to identify.

Go back
829.0, 101.0
30.0, 30.0

p33

p33

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c96 : 1
stoichiometry:c97 : 1
stoichiometry:c98 : 1
stoichiometry:c99 : 1

m36*m40*m38*0.1

nodelay

--

true

0

false

PMID: 8981359 These results suggest that, in response to CSF-1, PI3-kinase is tyrosine phosphorylated, and that other proteins associate with PI3-kinase, in addition to c-fms, to form a complex.

Go back
285.0, 689.0
29.0, 29.0

p34

p34

cso30:i:CE_DNAReplication

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c100 : 1
stoichiometry:c102 : 1
stoichiometry:c103 : 1
stoichiometry:c101 : 1

m42*m5*0.1

nodelay

--

true

0

false

PMID: 8981359 In contrast, rapamycin, an inhibitor of S6 kinase, inhibited CSF-1-induced DNA synthesis in BAC1.2F5 cells, suggesting that this kinase may be a part of the critical signaling pathway(s).

Go back
537.0, 565.0
30.0, 30.0

p35

p35

cso30:i:CE_DNAReplication

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c104 : 1
stoichiometry:c105 : 1
stoichiometry:c106 : 1
stoichiometry:c107 : 1
stoichiometry:c108 : 1
stoichiometry:c109 : 1

m42*m5*m35*0.1

nodelay

--

true

0

false

PMID: 8981359 However, there was a synergistic inhibition of DNA synthesis by the combination of wortmannin and rapamycin.

Go back
661.0, 905.0
30.0, 30.0

p36

p36

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c110 : 1
stoichiometry:c111 : 1
stoichiometry:c112 : 1

m5*m1357*0.1

nodelay

--

true

0

false

PMID: 8981359 These results suggest that STAT1 and STAT3 are activated in the BAC1.2F5 cells in response to CSF-1.

Go back
649.0, 1009.0
30.0, 30.0

p36

p37

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c113 : 1
stoichiometry:c114 : 1
stoichiometry:c115 : 1

m5*m1360*0.1

nodelay

--

true

0

false

PMID: 8981359 These results suggest that STAT1 and STAT3 are activated in the BAC1.2F5 cells in response to CSF-1.

Go back
238.0, 1002.0
27.0, 27.0

p38

p38

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c116 : 1
stoichiometry:c117 : 1
stoichiometry:c118 : 1

m13*m47*0.1

nodelay

--

true

0

false

PMID: 8981359 JAK kinases can be activated by IFNa/b or IFNg, and the presumed substrates for these kinases are the STAT proteins.

Go back
358.0, 1002.0
27.0, 27.0

p38

p39

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c119 : 1
stoichiometry:c120 : 1
stoichiometry:c121 : 1

m9*m47*0.1

nodelay

--

true

0

false

PMID: 8981359 JAK kinases can be activated by IFNa/b or IFNg, and the presumed substrates for these kinases are the STAT proteins.

Go back
829.0, 725.0
29.0, 29.0

p4

p4

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c8 : 1
stoichiometry:c9 : 1
stoichiometry:c136 : 1

m5*m11*0.1

nodelay

--

true

0

false

PMID: 8981359 We confirmed that CSF-1 could also induce low levels of IFNa/b production, as a cell-associated activity, in CBA BMM cell cultures.

Go back
887.0, 539.0
25.0, 25.0

p40

p40

cso30:i:ME_Phosphorylation

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c78 : 1
stoichiometry:c79 : 1
stoichiometry:c122 : 1

m38*m132*0.1

nodelay

--

true

0

false

PMID: 8981359 We also have evidence that Tyk2 is tyrosine phosphorylated after c-fms activation.

Go back
459.0, 1027.0
25.0, 25.0

p41

p41

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c123 : 1
stoichiometry:c124 : 1
stoichiometry:c125 : 1

m48*m49*0.1

nodelay

--

true

0

false

PMID: 8981359 JAK kinases can be activated by IFNa/b or IFNg, and the presumed substrates for these kinases are the STAT proteins. The STAT proteins can form homodimers or heterodimers when they are tyrosine phosphorylated, and they can effect DNA transcription through certain DNA response elements in IFN-responsive genes.

Go back
563.0, 1023.0
25.0, 25.0

p42

p42

cso30:i:ME_Dimerization

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c126 : 1
stoichiometry:c127 : 1

m63*0.1

nodelay

--

true

0

false

PMID: 8981359 JAK kinases can be activated by IFNa/b or IFNg, and the presumed substrates for these kinases are the STAT proteins. The STAT proteins can form homodimers or heterodimers when they are tyrosine phosphorylated, and they can effect DNA transcription through certain DNA response elements in IFN-responsive genes.

Go back
588.0, 456.0
24.0, 24.0

p43

p43

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c132 : 1
stoichiometry:c129 : 1

m66*0.1

nodelay

--

true

0

false

PMID: 8981359 JAK kinases can be activated by IFNa/b or IFNg, and the presumed substrates for these kinases are the STAT proteins. The STAT proteins can form homodimers or heterodimers when they are tyrosine phosphorylated, and they can effect DNA transcription through certain DNA response elements in IFN-responsive genes.

Go back
727.0, 475.0
26.0, 26.0

p44

p44

cso30:i:ME_Binding

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c128 : 1
stoichiometry:c130 : 1
stoichiometry:c131 : 1

m64*m65*0.1

nodelay

--

true

0

false

PMID: 8981359 JAK kinases can be activated by IFNa/b or IFNg, and the presumed substrates for these kinases are the STAT proteins. The STAT proteins can form homodimers or heterodimers when they are tyrosine phosphorylated, and they can effect DNA transcription through certain DNA response elements in IFN-responsive genes.

Go back
817.0, 861.0
29.0, 29.0

p4

p45

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c134 : 1
stoichiometry:c135 : 1
stoichiometry:c11 : 1

m93217*m5*0.1

nodelay

--

true

0

false

PMID: 8981359 We confirmed that CSF-1 could also induce low levels of IFNa/b production, as a cell-associated activity, in CBA BMM cell cultures.

Go back
1116.0, 884.0
23.0, 23.0

p46

p46

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c15 : 1
stoichiometry:c43 : 1
stoichiometry:c137 : 1

m70*m69*0.1

nodelay

--

true

0

false

PMID: 8981359 IFNalpha/beta bind their corresponding receptor.

Go back
794.0, 966.0
27.0, 27.0

p17

p48

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c148 : 1
stoichiometry:c149 : 1
stoichiometry:c150 : 1

m16*m11*0.1

nodelay

--

true

0

false

PMID: 8981359 We propose that LPS and TNFa inhibit DNA synthesis, at least in part, through their induction of endogenous type I IFN.

Go back
1058.0, 650.0
27.0, 27.0

p5

p5

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c12 : 1
stoichiometry:c10 : 1
stoichiometry:c13 : 1

m12*m68*0.1

nodelay

--

true

0

false

PMID: 8981359 IFNalpha/beta bind their corresponding receptor.

Go back
874.0, 1066.0
27.0, 27.0

p17

p50

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c155 : 1
stoichiometry:c156 : 1
stoichiometry:c157 : 1

m18*m93217*0.1

nodelay

--

true

0

false

PMID: 8981359 We propose that LPS and TNFa inhibit DNA synthesis, at least in part, through their induction of endogenous type I IFN.

Go back
862.0, 994.0
27.0, 27.0

p17

p6

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c142 : 1
stoichiometry:c143 : 1
stoichiometry:c144 : 1

m16*m93217*0.1

nodelay

--

true

0

false

PMID: 8981359 We propose that LPS and TNFa inhibit DNA synthesis, at least in part, through their induction of endogenous type I IFN.

Go back
495.0, 827.0
25.0, 25.0

p7

p7

cso30:i:CE_DNAReplication

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c19 : 1
stoichiometry:c17 : 1
stoichiometry:c20 : 1

1.0*0.1

nodelay

--

true

0

false

PMID: 8981359 The inhibitors that we have used include dimethylamiloride (DMA) (which inhibits the Na1/H1 antiporter), IFNg, lipopolysaccharide (LPS), tumor necrosis factor a (TNFa), and a number of compounds that raise intracellular cAMP levels. These agents, which apparently have nothing in common, all suppress macrophage DNA synthesis.

Go back
540.0, 1288.0
31.0, 31.0

p8

p8

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c21 : 1
stoichiometry:c22 : 1
stoichiometry:c23 : 1

m1639*m8*0.1

nodelay

--

true

0

false

PMID: 8981359 IFN-gamma binds its receptor.

Go back
423.0, 795.0
25.0, 25.0

p7

p9

cso30:i:CE_DNAReplication

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c24 : 1
stoichiometry:c49 : 1
stoichiometry:c30 : 1
stoichiometry:c25 : 1

m5*0.1

nodelay

--

true

0

false

PMID: 8981359 The inhibitors that we have used include dimethylamiloride (DMA) (which inhibits the Na1/H1 antiporter), IFNg, lipopolysaccharide (LPS), tumor necrosis factor a (TNFa), and a number of compounds that raise intracellular cAMP levels. These agents, which apparently have nothing in common, all suppress macrophage DNA synthesis. In a BAC1.2F5 cell line containing the control vector, the addition of IFNg or 8Br-cAMP inhibited the increase in DNA synthesis in response to CSF-1 PMID: 8981359 Studies were done to determine the effects of LPS, TNFa, IFNg, and 8Br-cAMP on the proliferation of BMM from wild-type mice compared with cells from the IFNAR-1 2/2 mice. As before, all agents suppressed DNAsynthesis in the wild-type system.

Go back
1076.324058133142, 481.0

c1

c1

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1085.6197177650145, 683.531325116055

c10

c10

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
137.0, 719.7441075202801

c100

c100

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
314.0, 708.0

c101

c101

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
143.0, 706.612411978035

c102

c102

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
321.9473242898715, 626.0

c103

c103

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
570.3805031059474, 255.0

c104

c104

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
143.0, 586.3222552562153

c105

c105

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
137.0, 593.0779474617779

c106

c106

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
574.9595173105159, 581.8037936200275

c107

c107

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
556.8223549478929, 129.0

c108

c108

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
492.7611526967923, 595.0

c109

c109

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
846.0, 834.1198975417233

c11

c11

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
696.809245172503, 639.0

c110

c110

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
504.0, 922.8110856104607

c111

c111

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
523.1455344671748, 927.0

c112

c112

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
681.0409061947561, 643.0

c113

c113

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
671.448073443305, 1046.616228490282

c114

c114

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
679.0, 1032.0

c115

c115

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
272.4444685502316, 734.0

c116

c116

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
255.15563384883419, 865.0

c117

c117

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
260.0, 1029.0

c118

c118

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
378.33774828479216, 1036.6508125684106

c119

c119

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
991.0, 684.6533910434308

c12

c12

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
284.0, 865.0

c120

c120

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
325.3670438189189, 1029.0

c121

c121

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
901.0, 564.0

c122

c122

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
334.0, 1049.122885527453

c123

c123

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
472.0, 1060.0

c124

c124

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
484.0, 1052.0

c125

c125

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
557.0, 1055.6921915811265

c126

c126

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
588.0, 1009.5172413793103

c127

c127

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
628.0, 508.7923198814722

c128

c128

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
571.567241614284, 448.5685159055888

c129

c129

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1006.426494172929, 674.0

c13

c13

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
705.0, 439.0

c130

c130

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
708.7249260681654, 479.079787787583

c131

c131

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
620.0, 468.0

c132

c132

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
732.0, 758.0

c134

c134

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
845.22846762196, 649.0

c135

c135

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
858.0, 741.0

c136

c136

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1005.8132665336364, 821.1927794053147

c137

c137

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
579.936278450915, 731.0

c139

c139

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
588.9980483043483, 716.1249390095109

c14

c14

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
861.0, 779.5570731934433

c140

c140

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
639.0, 1023.9036717503946

c142

c142

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
728.0, 758.0

c143

c143

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
889.0, 841.3874766427951

c144

c144

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
583.7847259761365, 808.8433777356972

c147

c147

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
639.0, 999.2030395517448

c148

c148

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
658.0, 822.0

c149

c149

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1000.0, 911.1318755781377

c15

c15

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
821.0, 782.1663866534142

c150

c150

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
840.0, 1100.1554175279994

c155

c155

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
727.0, 758.0

c156

c156

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
901.0, 845.5580668480437

c157

c157

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
592.4325502505212, 723.959256118263

c16

c16

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
523.6799645195888, 846.5677567204665

c17

c17

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
579.9997928279629, 804.0407103595721

c18

c18

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
353.0, 855.7567776747076

c19

c19

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
997.0, 529.0

c2

c2

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
491.8255305823146, 770.7889304845424

c20

c20

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
476.0, 1291.0

c21

c21

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
547.0, 1222.0

c22

c22

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
448.22830599112564, 1217.0207772785604

c23

c23

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
429.0, 823.9992137718218

c24

c24

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
448.0, 768.5718030173492

c25

c25

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
631.0, 1285.0

c26

c26

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
694.3861999450876, 1214.0

c27

c27

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
643.3370149585768, 1222.722373185794

c28

c28

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
337.0, 329.0

c29

c29

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1010.7257215188587, 576.0

c3

c3

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
235.0, 823.653875120043

c30

c30

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
769.0, 1275.2976528023867

c31

c31

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
874.4829175920399, 1156.0

c32

c32

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
839.8570997301327, 1231.4724146788087

c33

c33

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
231.0, 218.94506434836973

c34

c34

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
504.7911752716327, 767.22846762196

c35

c35

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
752.8271602636626, 1020.6539535080954

c36

c36

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
735.0, 970.795129565557

c39

c39

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
790.7937445760541, 577.8048671649809

c4

c4

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
670.0, 822.0

c42

c42

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1132.884800204972, 851.0

c43

c43

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
830.0, 940.9803336679332

c44

c44

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
401.18956777834734, 628.9955054820902

c45

c45

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
420.9981638976131, 612.1713892263774

c46

c46

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
389.884800204972, 572.7748008455096

c47

c47

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
455.5894663844041, 629.0

c49

c49

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
533.5027871695181, 484.7763617719803

c5

c5

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
332.0, 192.0

c50

c50

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
279.0, 143.0

c51

c51

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
333.0, 117.99334442480462

c52

c52

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
332.0, 250.0

c53

c53

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
345.37187404065014, 335.69975502333403

c54

c54

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
345.0, 283.2262082614183

c55

c55

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
349.0, 218.99391143541808

c56

c56

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
408.3330443576975, 120.0

c57

c57

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
422.19409903942767, 221.08451601761527

c58

c58

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
419.0, 135.05351674454224

c59

c59

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
592.8104426124714, 627.0

c6

c6

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
548.3377268214706, 135.0

c60

c60

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
561.0, 195.20394304577533

c61

c61

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
561.0, 230.0

c62

c62

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
516.8002105814442, 344.0

c63

c63

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
509.0, 399.0

c64

c64

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
473.0, 295.0

c65

c65

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
260.0, 146.0

c66

c66

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
267.0, 581.0

c67

c67

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
262.0, 146.0

c68

c68

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
308.0, 521.0

c69

c69

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
509.20614945095116, 723.0

c7

c7

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
264.0, 146.0

c70

c70

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
355.0, 493.0

c71

c71

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
410.8630022128471, 218.9057940525098

c72

c72

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
408.0793163436434, 218.99921353738844

c73

c73

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
588.9033078612182, 719.8741783230853

c74

c74

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
877.0, 455.0

c78

c78

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
872.0, 524.0

c79

c79

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
864.2469504755443, 637.0

c8

c8

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
675.0, 129.0

c87

c87

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
777.8133514099601, 235.03266315304202

c88

c88

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
711.799221533699, 224.0

c89

c89

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
671.0, 747.5872438429751

c9

c9

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
754.0, 338.0

c90

c90

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
792.3042819623698, 401.9887054413853

c91

c91

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
788.0, 390.0

c92

c92

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
878.4434204348745, 283.6177225322558

c93

c93

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
876.7988760535901, 199.0

c94

c94

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
801.6403967982608, 273.0

c95

c95

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
701.0, 135.51950036023962

c96

c96

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
789.0, 138.68049136653204

c97

c97

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
845.7165329735886, 138.96784666630577

c98

c98

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
747.9282586084793, 103.06897868878373

c99

c99

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back