Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Amino Acid Sequence
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Cells, Cultured
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Enzyme Activation
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GRB2 Adaptor Protein
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Humans
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In Vitro Techniques
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Macromolecular Substances
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Macrophage Colony-Stimulating Factor / pharmacology*
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Membrane Proteins / metabolism*
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Molecular Sequence Data
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Peptides / chemistry
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Peptides / metabolism
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Phosphatidylinositol 3-Kinases
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Phosphotransferases (Alcohol Group Acceptor) / metabolism*
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Protein Binding
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Proteins / metabolism*
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Proto-Oncogene Proteins p21(ras) / metabolism
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Receptor, Macrophage Colony-Stimulating Factor / metabolism*
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Signal Transduction
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Son of Sevenless Proteins
Substances
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Adaptor Proteins, Signal Transducing
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GRB2 Adaptor Protein
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GRB2 protein, human
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Macromolecular Substances
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Membrane Proteins
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Peptides
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Proteins
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Son of Sevenless Proteins
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Macrophage Colony-Stimulating Factor
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Phosphatidylinositol 3-Kinases
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Phosphotransferases (Alcohol Group Acceptor)
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Receptor, Macrophage Colony-Stimulating Factor
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HRAS protein, human
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Proto-Oncogene Proteins p21(ras)