Signaling by phosphoinositide-3,4,5-trisphosphate through proteins containing pleckstrin and Sec7 homology domains
Program in Molecular Medicine; Department of Biochemistry and Molecular Biology
1-Phosphatidylinositol 3-Kinase; ADP-Ribosylation Factor 1; ADP-Ribosylation Factors; Adipocytes; Amino Acid Sequence; Animals; Antigens, CD18; Blood Proteins; Brain Chemistry; Cell Adhesion Molecules; Cell Membrane; Cells, Cultured; Cloning, Molecular; DNA, Complementary; Fungal Proteins; GTP-Binding Proteins; *Guanine Nucleotide Exchange Factors; Humans; Mice; Molecular Sequence Data; Phosphatidylinositol Phosphates; *Phosphoproteins; Phosphorylation; Phosphotransferases (Alcohol Group Acceptor); Receptors, Cytoplasmic and Nuclear; Recombinant Fusion Proteins; Sequence Homology, Amino Acid; *Signal Transduction
Life Sciences | Medicine and Health Sciences
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.
Science. 1997 Mar 28;275(5308):1927-30.
Science (New York, N.Y.)
Klarlund JK, Guilherme AL, Holik J, Virbasius JV, Chawla A, Czech MP. (1997). Signaling by phosphoinositide-3,4,5-trisphosphate through proteins containing pleckstrin and Sec7 homology domains. Open Access Articles. Retrieved from https://escholarship.umassmed.edu/oapubs/1646