Transforming potential of the c-fms proto-oncogene (CSF-1 receptor)

Roussel, Martine F.; Dull, Thomas J.; Rettenmier, Carl W.; Ralph, Peter; Ullrich, Axel; Sherr, Charles J.

doi:10.1038/325549a0

Cited by 336 publications

(231 citation statements)

References 24 publications

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“…By contrast, studies on other tyrosine kinases have implicated the terminal tyrosine in the negative control of kinase signaling functions (i.e. the insulin receptor, CSF-1 receptor, Src nonreceptor tyrosine kinase; Roussel et al, 1987;Ellis et al, 1986;Thies et al, 1989;Cantley et al, 1991;Herbst et al, 1995;. For example, an insulin receptor mutant lacking C-terminal Tyr1316 and Tyr1322 demonstrates increased insulin induced mitogenesis and mitogen activated protein kinase activity (Ando et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

Determinants for transformation induced by the Axl receptor tyrosine kinase

et al. 1998

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The Axl receptor tyrosine kinase is a transforming oncogene in NIH3T3 cells. In order to de®ne structural requirements of the Axl receptor necessary for transformation we passaged recombinant retroviruses carrying the axl cDNA in NIH3T3 cells, generating randomly mutated axl variants. Using this strategy, we have isolated three axl viral strains (1B1, SV8, and FFa4) that show augmented 3T3 cell transforming capacity associated with elevated p140 Axl . Upon sequencing, the 1B1 and SV8 proviruses possessed only silent mutations, making p140 Axl overexpression the most likely explanation for their increased transformation activity. However, the characterization of FFa4 revealed a deletion of sequences encoding the carboxy-terminal 45 amino acids leading to the generation of a chimeric transcript comprised of a truncated Axl receptor with a segment of the 3' UTR region. Mutational analysis revealed that the transforming activity of FFa4 was speci®c to the formation of the chimeric receptor rather than to the carboxyl-terminal truncation. Intriguingly, none of the viral strains were able to transform the murine cell lines NR-6 and 32D despite equivalent expression of surface p140 Axl protein. Further analysis showed that Axl's transforming potential is dependent on the host cell type, the presence of a putative pp190 as a facilitator for transformation, and the level of p140 Axl expression. Taken together, these results underscore the complexity of Axl biology which is dependent on receptor stoichiometry and the cellular background.

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Section: Discussionmentioning

confidence: 99%

Determinants for transformation induced by the Axl receptor tyrosine kinase

et al. 1998

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“…These cells proliferate in the presence of FCS and normally display contact inhibition. In the presence of M-CSF, rodent fibroblasts that express FMS (Rat-2cfms) become transformed and resistant to contact inhibition and so grow to a higher cell number (Roussel et al, 1987;Baker et al, 1994). Figure 3c shows that the proliferation of Rat-2c-fms cells in the absence of M-CSF was relatively unaffected by imatinib.…”

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confidence: 85%

FMS receptor for M-CSF (CSF-1) is sensitive to the kinase inhibitor imatinib and mutation of Asp-802 to Val confers resistance

et al. 2005

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The kinase inhibitor imatinib is used in the treatment of chronic myeloid leukaemia, where it targets the intracellular Bcr-Abl tyrosine kinase, and gastrointestinal stromal tumours, where it targets either the KIT or PDGF tyrosine kinase receptors. Here, we report that imatinib is also an effective inhibitor of the closely related FMS receptor for macrophage colony stimulating factor and that mutation of Asp 802 of FMS to Val confers imatinib resistance. Imatinib readily reverted the transformed phenotype of haemopoietic and fibroblast cell lines that express the oncogene v-fms and also inhibited the growth of the Bacl.2F5 macrophage cell line. The cellular IC 50 value of imatinib for FMS was similar to those for BcrAbl and KIT. Consequently, imatinib may also prove effective for the treatment of diseases whose progression is dependent upon macrophage-colony stimulating factor, this includes certain aspects of cancer and inflammation.

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“…Since most ®broblasts express endogenous PDGF receptors, we designed chimeric receptors in which the extracellular ligand binding domain of the human bPDGF receptor was replaced with that of the human colony stimulating factor-1 (CSF-1) receptor (Figure 3a) (Sherr et al, 1985). This allowed us to speci®cally stimulate the chimeric receptor (CSF/PDGF receptor) with human CSF-1 without activating endogenous PDGF receptors (Roussel et al, 1987). When expressed in NIH3T3 cells, the CSF/PDGF receptor chimera initiated identical STAT activation ( Figure 3b), protein tyrosine phosphorylation (Figure 4a) and mitogenic response (Figure 6b) to the endogenous PDGF receptor.…”

Section: Activation Of Stats In ®Broblasts In the Absence Of Detectabmentioning

confidence: 99%

STAT activation by the PDGF receptor requires juxtamembrane phosphorylation sites but not Src tyrosine kinase activation

1999

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Activation of the platelet-derived growth factor (PDGF) receptor tyrosine kinase induces tyrosine phosphorylation of Signal Transducer and Activator of Transcription (STAT) proteins. Since the PDGF receptor also activates the Src tyrosine kinase, it is possible that Src mediates tyrosine phosphorylation of STATs in PDGFtreated cells. Consistent with a role for Src in STAT activation, we found that a PDGF receptor juxtamembrane tyrosine residue required for Src activation is necessary and su cient for activation of STATs 1 and 3. To test the Src requirement further, we made other mutations in the PDGF receptor juxtamembrane region that increased or decreased Src binding. In epithelial and ®broblast cells, PDGF activated STAT1, 3 and 6 in the absence of detectable binding and activation of Src. In addition, PDGF induced c-myc RNA expression and DNA synthesis even though Src was not detectably activated. The activation of MAP kinase and the induction of c-fos gene expression both correlated with STAT but not Src activation by the receptor. We conclude that juxtamembrane tyrosine phosphorylation is necessary for both Src tyrosine kinase and STAT activation by the bPDGF receptor, but that both processes are regulated independently by this region.

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Transforming potential of the c-fms proto-oncogene (CSF-1 receptor)

Cited by 336 publications

References 24 publications

Determinants for transformation induced by the Axl receptor tyrosine kinase

Determinants for transformation induced by the Axl receptor tyrosine kinase

FMS receptor for M-CSF (CSF-1) is sensitive to the kinase inhibitor imatinib and mutation of Asp-802 to Val confers resistance

STAT activation by the PDGF receptor requires juxtamembrane phosphorylation sites but not Src tyrosine kinase activation

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