PMID- 10356364 OWN - NLM STAT- MEDLINE DCOM- 20000828 LR - 20091119 IS - 1522-4724 (Print) IS - 1522-4724 (Linking) VI - 1 IP - 2 DP - 1999 May TI - Expression of a Y559F mutant CSF-1 receptor in M1 myeloid cells: a role for Src kinases in CSF-1 receptor-mediated differentiation. PG - 144-52 AB - We have established two M1 myeloid cell lines, M1/WT cells overexpressing the wild-type CSF-1 receptor and M1/Y559F cells expressing a specific tyrosine mutant. M1/WT cells differentiated in response to CSF-1, with a reduction in their proliferative capacity. CSF-1-mediated differentiation was partially abrogated in the M1/Y559F cells, with a less marked reduction in proliferative capacity. The Src tyrosine kinases c-Src, c-Yes, c-Fyn, and c-Hck were tyrosine phosphorylated in the M1/WT cells in response to CSF-1 and bound to the WT CSF-1R through their SH2 domains. Binding of the Src kinases to the CSF-1 receptor was greatly reduced in the M1/Y559F cells. CSF-1-mediated activation of STAT3 was also abrogated in the M1/Y559F cell line. Treatment of M1/WT cells with the Src family inhibitor PP2 resulted in an inhibition of CSF-1-mediated differentiation, equivalent to that observed in the M1/Y559F cells. These data suggest that the reduced Src binding observed in the M1/Y559F cells may contribute to their reduced ability to differentiate. FAU - Marks, D C AU - Marks DC AD - Inflammation Research Centre, Department of Medicine, University of Melbourne, Parkville, Victoria, Australia. x.csar@medicine.unimelb.edu.au FAU - Csar, X F AU - Csar XF FAU - Wilson, N J AU - Wilson NJ FAU - Novak, U AU - Novak U FAU - Ward, A C AU - Ward AC FAU - Kanagasundarum, V AU - Kanagasundarum V FAU - Hoffmann, B W AU - Hoffmann BW FAU - Hamilton, J A AU - Hamilton JA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Mol Cell Biol Res Commun JT - Molecular cell biology research communications : MCBRC JID - 100889076 RN - 0 (DNA-Binding Proteins) RN - 0 (Enzyme Inhibitors) RN - 0 (STAT3 Transcription Factor) RN - 0 (Stat3 protein, mouse) RN - 0 (Trans-Activators) RN - 81627-83-0 (Macrophage Colony-Stimulating Factor) RN - EC 2.7.10.1 (Receptor, Macrophage Colony-Stimulating Factor) RN - EC 2.7.10.2 (src-Family Kinases) SB - IM MH - Animals MH - Cell Differentiation MH - DNA-Binding Proteins/*metabolism MH - Enzyme Inhibitors/pharmacology MH - Leukemia, Myeloid, Acute MH - Macrophage Colony-Stimulating Factor/pharmacology MH - Mice MH - Mutation MH - Phosphorylation MH - Precipitin Tests MH - Receptor, Macrophage Colony-Stimulating Factor/genetics/*metabolism MH - STAT3 Transcription Factor MH - Signal Transduction MH - Trans-Activators/*metabolism MH - Tumor Cells, Cultured MH - src-Family Kinases/antagonists & inhibitors/*metabolism EDAT- 1999/11/30 09:00 MHDA- 2000/09/02 11:01 CRDT- 1999/11/30 09:00 PHST- 1999/11/30 09:00 [pubmed] PHST- 2000/09/02 11:01 [medline] PHST- 1999/11/30 09:00 [entrez] AID - S152247249990123X [pii] AID - 10.1006/mcbr.1999.0123 [doi] PST - ppublish SO - Mol Cell Biol Res Commun. 1999 May;1(2):144-52. doi: 10.1006/mcbr.1999.0123.