Abstract
Signal transmission by many cell surface receptors results in the activation of phosphoinositide (PI) 3-kinases that phosphorylate the 3' position of polyphosphoinositides. From a screen for mouse proteins that bind phosphoinositides, the protein GRP1was identified. GRP1 binds phosphatidylinositol-3,4,5-trisphosphate [PtdIns(3,4, 5)P3] through a pleckstrin homology (PH) domain and displays a region of high sequence similarity to the yeast Sec7 protein. The PH domain of the closely related protein cytohesin-1, which, through its Sec7 homology domain, regulates integrin beta2 and catalyzes guanine nucleotide exchange of the small guanine nucleotide-binding protein ARF1, was also found to specifically bind PtdIns(3,4,5)P3. GRP1 and cytohesin-1 appear to connect receptor-activated PI 3-kinase signaling pathways with proteins that mediate biological responses such as cell adhesion and membrane trafficking.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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ADP-Ribosylation Factor 1
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ADP-Ribosylation Factors
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Adipocytes / chemistry
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Amino Acid Sequence
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Animals
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Blood Proteins / chemistry*
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Brain Chemistry
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CD18 Antigens / metabolism
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Cell Adhesion Molecules / chemistry
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Cell Adhesion Molecules / metabolism*
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Cell Membrane / metabolism
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Cells, Cultured
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Cloning, Molecular
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DNA, Complementary
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Fungal Proteins / chemistry*
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GTP-Binding Proteins / metabolism
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Guanine Nucleotide Exchange Factors*
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Humans
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Mice
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Molecular Sequence Data
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Phosphatidylinositol 3-Kinases
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Phosphatidylinositol Phosphates / metabolism*
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Phosphoproteins*
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Phosphorylation
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Phosphotransferases (Alcohol Group Acceptor) / metabolism*
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Receptors, Cytoplasmic and Nuclear / metabolism
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / metabolism
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Sequence Homology, Amino Acid
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Signal Transduction*
Substances
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Blood Proteins
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CD18 Antigens
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Cell Adhesion Molecules
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DNA, Complementary
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Fungal Proteins
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Guanine Nucleotide Exchange Factors
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Phosphatidylinositol Phosphates
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Phosphoproteins
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Receptors, Cytoplasmic and Nuclear
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Recombinant Fusion Proteins
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Sec7 guanine nucleotide exchange factors
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cytohesin-1
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phosphatidylinositol 3,4,5-triphosphate
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phosphatidylinositol receptors
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platelet protein P47
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Phosphatidylinositol 3-Kinases
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Phosphotransferases (Alcohol Group Acceptor)
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GTP-Binding Proteins
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ADP-Ribosylation Factor 1
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ADP-Ribosylation Factors