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.
Kharbanda
S
S
Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Saleem
A
A
Yuan
Z
Z
Emoto
Y
Y
Prasad
K V
KV
Kufe
D
D
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D001665:Binding Sites; D015815:Cell Adhesion Molecules / Q000097:blood* / Q000302:isolation & purification; D034281:Dynamins; D004591:Electrophoresis, Polyacrylamide Gel; D066246:ErbB Receptors / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051380:GRB2 Adaptor Protein; D020558:GTP Phosphohydrolases / Q000097:blood* / Q000302:isolation & purification; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008870:Microtubules / Q000378:metabolism; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000097:blood* / Q000302:isolation & purification; D011506:Proteins / Q000302:isolation & purification / Q000378:metabolism*; D011972:Receptor, Insulin / Q000097:blood; D011994:Recombinant Proteins / Q000494:pharmacology
D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D011506:Proteins; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D020558:GTP Phosphohydrolases; D034281:Dynamins