Stimulation of human monocytes with macrophage colony-stimulating factor induces a Grb2-mediated association of the focal adhesion kinase pp125FAK and dynamin.

Macrophage colony-stimulating factor (M-CSF) is required for the growth and differentiation of mononuclear phagocytes. In the present studies using human monocytes, we show that M-CSF induces interaction of the Grb2 adaptor protein with the focal adhesion kinase pp125FAK. The results demonstrate that tyrosine-phosphorylated pp125FAK directly interacts with the SH2 domain ...
of Grb2. The findings indicate that a pYENV site at Tyr-925 in pp125FAK is responsible for this interaction. We also demonstrate that the Grb2-FAK complex associates with the GTPase dynamin. Dynamin interacts with the SH3 domains of Grb2 and exhibits M-CSF-dependent tyrosine phosphorylation in association with pp125FAK. These findings suggest that M-CSF-induced signaling involves independent Grb2-mediated pathways, one leading to Ras activation and another involving pp125FAK and a GTPase implicated in receptor internalization.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Binding Sites, Cell Adhesion Molecules, Dynamins, Electrophoresis, Polyacrylamide Gel, ErbB Receptors, Focal Adhesion Kinase 1, Focal Adhesion Protein-Tyrosine Kinases, GRB2 Adaptor Protein, GTP Phosphohydrolases, Humans, Macrophage Colony-Stimulating Factor, Microtubules, Molecular Sequence Data, Molecular Weight, Monocytes, Protein-Tyrosine Kinases, Proteins, Receptor, Insulin, Recombinant Proteins
Proc. Natl. Acad. Sci. U.S.A.
Date: Jun. 20, 1995
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