Monocyte colony-stimulating factor stimulates binding of phosphatidylinositol 3-kinase to Grb2.Sos complexes in human monocytes.

Monocyte colony-stimulating factor (M-CSF) is required for the proliferation of mononuclear phagocytes. The activated M-CSF receptor associates with phosphatidylinositol 3-kinase (PI 3-kinase). In the present studies, we demonstrate that M-CSF also induces direct interaction of PI 3-kinase (p85 alpha subunit) with the SH2/SH3 adaptor protein Grb2. Tyrosine-phosphorylated PI 3-kinase interacts with the SH2 domain of Grb2. A pYRNE (pY408) site in PI 3-kinase is potentially involved in this interaction. The results also demonstrate that the PI 3-kinase.Grb2 complex associates with the guanine nucleotide exchange protein Sos. Since Sos binds to the SH3 domains of Grb2 and thereby associates with Ras at the cell membrane, formation of the PI 3-kinase.Grb2.Sos complex provides a potential mechanism for growth factor-induced interactions of PI 3-kinase and Ras.