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.

PMID: 8981359 LPS binds its corresponding receptor

PMID: 8981359 TNF-alpha binds its corresponding receptor.

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.

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.

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

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

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

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

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 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.

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, 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 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.

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.

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.

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

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

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

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

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.

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).

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

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

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

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

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

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.

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

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.

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.

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.

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.

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.

PMID: 8981359 IFNalpha/beta bind their corresponding receptor.

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

PMID: 8981359 IFNalpha/beta bind their corresponding receptor.

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

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

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.

PMID: 8981359 IFN-gamma binds its receptor.

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.