MONOCYTE COLONY-STIMULATING FACTOR STIMULATES BINDING OF PHOSPHATIDYLINOSITOL 3-KINASE TO GRB2-CENTER-DOT-SOS COMPLEXES IN HUMAN MONOCYTES

Monocyte colony-stimulating factor (M-CSF) is required for the prolife ration of mononuclear phagocytes. The activated M-CSF receptor associa tes with phosphatidylinositol 3-kinase (PI 3-kinase). In the present s tudies, we demonstrate that M-CSF also induces direct interaction of P I 3-kinase (p85 alpha subunit) with the SH2/SH3 adaptor protein Grb2. Tyrosine-phosphorylated PI 3-kinase interacts with the SH2 domain of G rb2. A pYRNE (pY408) site in PI 3-kinase is potentially involved in th is interaction. The results also demonstrate that the PI 3-kinase . Gr b2 complex associates with the guanine nucleotide exchange protein Sos . Since Sos binds to the SH3 domains of Grb2 and thereby associates wi th Pas at the cell membrane, formation of the PI 3-kinase . Grb2 . Sos complex provides a potential mechanism for growth factor-induced inte ractions of PI 3-kinase and Pas.