Marks D C, Csar X F, Wilson N J, Novak U, Ward A C, Kanagasundarum V, Hoffmann B W, Hamilton J A
Inflammation Research Centre, Department of Medicine, University of Melbourne, Parkville, Victoria, Australia.
Mol Cell Biol Res Commun. 1999 May;1(2):144-52. doi: 10.1006/mcbr.1999.0123.
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.
我们建立了两种M1髓样细胞系，即过表达野生型CSF-1受体的M1/WT细胞和表达特定酪氨酸突变体的M1/Y559F细胞。M1/WT细胞对CSF-1有反应而发生分化，其增殖能力降低。CSF-1介导的分化在M1/Y559F细胞中部分被消除，增殖能力的降低不太明显。Src酪氨酸激酶c-Src、c-Yes、c-Fyn和c-Hck在M1/WT细胞中因CSF-1而发生酪氨酸磷酸化，并通过其SH2结构域与野生型CSF-1R结合。在M1/Y559F细胞中，Src激酶与CSF-1受体的结合大大减少。CSF-1介导的STAT3激活在M1/Y559F细胞系中也被消除。用Src家族抑制剂PP2处理M1/WT细胞导致CSF-1介导的分化受到抑制，这与在M1/Y559F细胞中观察到的情况相当。这些数据表明，在M1/Y559F细胞中观察到的Src结合减少可能导致其分化能力降低。
