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
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
PubMed ID: 7597091
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