/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/8485905.csml - 2009.07.01.11:23

Original Literature	Model OverView
Publication Title CR3 (CD11b, CD18): a phagocyte and NK cell membrane receptor with multipleligand specificities and functions. Authors Ross GD, Vetvicka V. Affiliation Department of Microbiology and Immunology, University of Louisville, KY 40292. Abstract The C3 receptor CR3 is expressed on phagocytic cells, minor subsets of B and Tcells, and natural killer (NK) cells. It has important functions both as anadhesion molecule and a membrane receptor mediating recognition of diverseligands such as intercellular adhesion molecule-1 (ICAM-1) and fixed iC3b. Thereceptor is capable of undergoing an activation event that regulates both itsspecificity for various ligands and its ability to mediate phagocytosis orextracellular cytotoxicity. Certain bacteria express carbohydrates orlipopolysaccharides (LPS) that can bind to and activate CR3, allowing thereceptor to assume its activated state. Soluble beta-glucan derived from theyeast Saccharomyces cerevisiae is a particularly potent stimulator of CR3, andproduces an activated state of the receptor that permits neutrophil phagocytosisof iC3b-coated erythrocytes or NK, cell cytotoxicity of iC3b-coated tumourcells, that are normally resistant to NK cells. PMID 8485905

Model Detail

166.75, 76.99690800911759

856.2594311764528, 1243.2886940682085

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane

csml-variable:Double

false

infinite

unit

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189.0, 96.0

829.9775981223105, 1167.545103664102

e10

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytosol

csml-variable:Double

m10

false

infinite

unit

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968.5, 290.0

31.0, 60.0

Zymosan:CD11b:CD18

e11

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

p4 p9

csml-variable:Double

m11

false

infinite

unit

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1215.5, 282.0

41.0, 60.0

E.Coli

e12

cso30:c:Cell

cso30:i:CC_Extracellular

csml-variable:Double

m12

false

infinite

unit

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972.5, 394.0

31.0, 60.0

E.coli:CD11b:CD18

e13

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

csml-variable:Double

m13

false

infinite

unit

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1192.0, 412.6557657476353

48.39605554437512, 29.844234252364664

iC3b

e14

cso30:c:Protein

cso30:i:CC_Extracellular

csml-variable:Double

m14

false

infinite

unit

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972.5, 494.0

31.0, 60.0

iC3b:CD11b:CD18

e15

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

csml-variable:Double

m15

false

infinite

unit

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972.5, 102.0

31.0, 60.0

zymosan:CD11b{p}:CD18{p}

e16

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

p4 p9

csml-variable:Double

m16

false

infinite

unit

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329.0, 302.58

46.56, 34.92

PKC

e17

cso30:c:Protein

cso30:i:CC_Cytosol

p7 p4

csml-variable:Double

m17

false

infinite

unit

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882.0, 419.0

60.0, 34.0

staurosporine

e18

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

csml-variable:Double

m18

false

infinite

unit

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1222.0, 559.0

60.0, 34.0

LPS

e19

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

csml-variable:Double

m19

false

infinite

unit

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166.75, 76.99690800911759

856.2594311764528, 1243.2886940682085

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

csml-variable:Double

false

infinite

unit

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972.5, 602.0

31.0, 60.0

LPS:CD11b:CD18

e20

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

csml-variable:Double

m20

false

infinite

unit

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1251.0, 674.1748681898067

42.03866432337434, 27.325131810193323

lectin

e21

cso30:c:Protein

cso30:i:CC_Extracellular

csml-variable:Double

m21

false

infinite

unit

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972.5, 698.0

31.0, 60.0

lectin:CD11b:CD18

e22

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

csml-variable:Double

m22

false

infinite

unit

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1206.0, 112.14640772791307

52.465284765546386, 32.353592272086935

L-selectin

e23

cso30:c:Protein

cso30:i:CC_Extracellular

csml-variable:Double

m23

false

infinite

unit

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824.5, 70.0

31.0, 60.0

L-selectin:CD11b:CD18

e24

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

csml-variable:Double

m24

false

infinite

unit

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1214.0, 771.0

60.0, 34.0

glucans

e25

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

csml-variable:Double

m25

false

infinite

unit

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972.5, 794.0

31.0, 60.0

glucans:CD11b:CD18

e26

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

csml-variable:Double

m26

false

infinite

unit

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1325.0, 94.38461538461539

29.076923076923077, 43.615384615384606

MoAbOKM1

e27

cso30:c:Protein

cso30:i:CC_Cytosol

csml-variable:Double

m27

false

infinite

unit

Go back

586.0, 252.0

20.916744621141255, 48.26941066417212

tyrosine kinase

e28

cso30:c:Protein

cso30:i:CC_Cytosol

csml-variable:Double

m28

false

infinite

unit

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654.0, 355.0

60.0, 34.0

genistein

e29

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

csml-variable:Double

m29

false

infinite

unit

Go back

183.87518862352903, 94.12209663264667

822.0090539293948, 1209.0383168211513

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

csml-variable:Double

false

infinite

unit

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802.0, 651.0

60.0, 34.0

herbimycin A

e30

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

csml-variable:Double

m30

false

infinite

unit

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215.55678757705792, 124.09117672382234

758.6458560223374, 1149.1001566387988

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

csml-variable:Double

false

infinite

unit

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968.5, 198.0

39.0, 60.0

CD11b:CD18

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

p1 p2 p3 p5 p6 p7 p8

csml-variable:Double

false

infinite

unit

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331.0, 761.0

465.6500709748862, 422.29345356567933

e50

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelopeLumen

csml-variable:Double

m50

false

infinite

unit

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381.29367619468036, 771.0077409313898

272.27955732982184, 409.2864683429171

e51

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearPore

csml-variable:Double

m51

false

infinite

unit

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337.06992643728904, 766.6363602631969

453.51021810030846, 411.0207330392853

e52

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearInnerMembrane

csml-variable:Double

m52

false

infinite

unit

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337.93705878547314, 767.503492611381

451.7759534039399, 409.2864683429171

e53

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearLumen

csml-variable:Double

m53

false

infinite

unit

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331.0, 761.0

465.6500709748862, 422.29345356567933

e54

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearOuterMembrane

csml-variable:Double

m54

false

infinite

unit

Go back

331.0, 761.0

465.6500709748862, 422.29345356567933

e55

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleus

csml-variable:Double

m55

false

infinite

unit

Go back

337.93705878547314, 767.503492611381

451.7759534039399, 409.2864683429171

e56

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleoplasm

csml-variable:Double

m56

false

infinite

unit

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670.9158804881849, 934.4264696368292

29.091257918298922, 26.33524401024959

e57

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearBody

csml-variable:Double

m57

false

infinite

unit

Go back

594.6082338479803, 1055.8249983826097

82.37757307749382, 74.57338194383664

e58

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleolus

csml-variable:Double

m58

false

infinite

unit

Go back

331.0, 761.0

465.6500709748862, 422.29345356567933

e59

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelope

csml-variable:Double

m59

false

infinite

unit

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1310.0, 207.0

60.0, 34.0

Zymosan

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

csml-variable:Double

false

infinite

unit

Go back

440.7511016961721, 948.6637213250546

14.746453546866459, 7.100144300343119

e60

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Chromatin

csml-variable:Double

m60

false

infinite

unit

Go back

440.25867587120234, 927.4894108513561

50.4736470593979, 90.85256470691624

e61

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearChromosome

csml-variable:Double

m61

false

infinite

unit

Go back

461.43298634490145, 986.5805098477247

7.878813199515761, 7.8788131995157675

e62

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearCentromere

csml-variable:Double

m62

false

infinite

unit

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184.0, 77.0

839.7237354966342, 1189.8668429177399

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell

csml-variable:Double

false

infinite

unit

Go back

164.0, 70.0

805.5569854171277, 1169.6687428256696

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell_WithoutCellWall_

csml-variable:Double

false

infinite

unit

Go back

172.0, 91.0

801.8791759029863, 1154.3288303559784

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytoplasm

csml-variable:Double

false

infinite

unit

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1157.0, 213.0

21.0, 21.0

cso30:i:ME_Binding

cso30:i:CC_Extracellular

e5 e6 e27

e11

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c1 : 1
stoichiometry:c2 : 1
stoichiometry:c26 : 1
stoichiometry:c3 : 1

m5*m6*0.1

nodelay

true

false

PMID: 8485905, 3040333 Both zymosan (cell wall extract from the yeast Saccharomyces cereviseae) and Escherichia coli bind to resting CR3 and promote the phagocytically active state of CR3. beta-glucan component of zymosan, was responsible for CR3-dependent responses to iC3b-opsonized zymosan. CR3-dependent responses to fl-glucan were blocked by the CR3 alpha chain-specific MoAb OKMI.

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1117.0, 301.0

21.0, 21.0

cso30:i:ME_Binding

cso30:i:CC_Extracellular

e5 e12

e13

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c4 : 1
stoichiometry:c5 : 1
stoichiometry:c6 : 1

m5*m12*0.1

nodelay

true

false

PMID: 8485905 Both zymosan (cell wall extract from the yeast Saccharomyces cereviseae) and Escherichia coli bind to resting CR3 and promote the phagocytically active state of CR3.

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1112.0, 420.0

23.0, 23.0

cso30:i:ME_Binding

cso30:i:CC_Extracellular

e5 e14

e15

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c7 : 1
stoichiometry:c8 : 1
stoichiometry:c9 : 1

m5*m14*0.1

nodelay

true

false

PMID: 8485905, 833545, 573303, 7430626, 7252421, 7049467 Fixed iC3b on sheep erythrocytes (EC3bi) binds avidly to neutrophil, monocyte, and NK cell CR3, but does not trigger any cytotoxic reaction.

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899.0, 307.0

25.0, 25.0

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

e17 e18 e11

e16

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c12 : 1
stoichiometry:c13 : 1
stoichiometry:c10 : 1
stoichiometry:c20 : 1

m17*m11*0.1

nodelay

true

false

PMID: 8485905, 1976698, 1673986 CR3 is capable of mediating phagocytosis following protein kinase C (PKC)-dependent activation. Blockade of both PMA- induced phagocytosis and homotypic aggregation by the PKC inhibitor staurosporine suggests a similar activation pathway for these two CR3-dependent functions. Neutrophil aggregation and phagocytosis of EC3bi induced by PMA were blocked by staurosporine suggested that a PKC-associated phosphorylation event was required for CR3 activation. beta-glucan derived from zymosan binds to CR3 and activates the receptor via a phosphorylation event involving both PKC and a tyrosine kinase.

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1116.0, 564.0

23.0, 23.0

cso30:i:ME_Binding

cso30:i:CC_Extracellular

e19 e5

e20

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c15 : 1
stoichiometry:c16 : 1
stoichiometry:c14 : 1

m19*m5*0.1

nodelay

true

false

PMID: 8485905, 3537192 Lipopolysaccharide (LPS) on E. coli appears to bind to CR3 at a distinct site from beta-glucan and also stimulates CR3-dependent phagocytosis.

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1111.0, 675.0

25.0, 25.0

cso30:i:ME_Binding

cso30:i:CC_Extracellular

e5 e21

e22

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c17 : 1
stoichiometry:c18 : 1
stoichiometry:c19 : 1

m5*m21*0.1

nodelay

true

false

PMID: 8485905, 1682263 certain fimbriated strains of E. coli stimulate CR3- dependent phagocytosis by way of a mannose-specific lectin on the bacteria that binds to a carbohydrate on CR3.

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1139.0, 39.0

25.0, 25.0

cso30:i:ME_Binding

cso30:i:CC_Extracellular

e23 e5 e17

e24

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c21 : 1
stoichiometry:c28 : 1
stoichiometry:c32 : 1
stoichiometry:c23 : 1

m23*m5*m17*0.1

nodelay

true

false

PMID: 8485905, 1383326, 3283242, 1976698 Neutrophil homotypic aggregation requires PKC for exposure of a CR3 binding site for a counter-receptor on other neutrophils recently shown to be L-selectin.

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1107.0, 775.0

25.0, 25.0

cso30:i:ME_Binding

cso30:i:CC_Extracellular

e25 e5

e26

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c24 : 1
stoichiometry:c25 : 1
stoichiometry:c22 : 1

m25*m5*0.1

nodelay

true

false

PMID: 8485905, 2579146 soluble glucans from barley or laminarin bound weakly to CR3.

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819.0, 263.0

25.0, 25.0

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

e28 e29 e30 e11

e16

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c29 : 1
stoichiometry:c30 : 1
stoichiometry:c31 : 1
stoichiometry:c27 : 1
stoichiometry:c11 : 1

m28*m11*0.1

nodelay

true

false

PMID: 8485905 beta-glucan derived from zymosan binds to CR3 and activates the receptor via a phosphorylation event involving both PKC and a tyrosine kinase. glucan-induced phagocytosis of EC3bi is not only prevented by staurosporine,but it is also blocked by genistein or herbimycin A, two tyrosine kinase inhibitors.

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