Macrophage colony-stimulating factor receptor induces tyrosine phosphorylation of SKAP55R adaptor and its association with actin

The production, survival, and function of monocytes and macrophages are regulated by the macrophage colony-stimulating factor (M-CSF or CSF-1) through its tyrosine kinase receptor. M-CSF receptor activates multiple cytoplasmic pathways in which adaptor and scaffolding proteins play a central role. In this study, we showed that SKAP55-related (SKAP55R) adaptor protein is expressed in myeloid cells and macrophages and is rapidly and transiently tyrosine-phosphorylated in response to M-CSF. M-CSF induced SKAP55R association with other tyrosine-phosphorylated proteins and with actin. When overexpressed in myeloid cells, SKAP55R decreased M-CSF-dependent proliferation without affecting differentiation. Altogether, these results demonstrate that SKAP55R adaptor is implicated in the M-CSF signaling pathway and suggest its role as a negative regulator of growth. Moreover, specific association between SKAP55R and actin support the idea that SKAP55R is implicated in the regulation of actin dynamics under the control of M-CSF.