Signaling by phosphoinositide-3,4,5-trisphosphate through proteins containing pleckstrin and Sec7 homology domains.
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.
Klarlund
J K
JK
Program in Molecular Medicine and Department of Biochemistry and Molecular Biology, University of Massachusetts Medical Center, 373 Plantation Street, Worcester, MA 01605, USA.
Guilherme
A
A
Holik
J J
JJ
Virbasius
J V
JV
Chawla
A
A
Czech
M P
MP
D020823:ADP-Ribosylation Factor 1; D020727:ADP-Ribosylation Factors; D017667:Adipocytes / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D001798:Blood Proteins / Q000737:chemistry*; D001923:Brain Chemistry; D018821:CD18 Antigens / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary; D005656:Fungal Proteins / Q000737:chemistry*; D019204:GTP-Binding Proteins / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D010750:Phosphoproteins; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D001798:Blood Proteins; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D005656:Fungal Proteins; D020662:Guanine Nucleotide Exchange Factors; D018129:Phosphatidylinositol Phosphates; D010750:Phosphoproteins; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; C066755:Sec7 guanine nucleotide exchange factors; C100723:cytohesin-1; C060974:phosphatidylinositol 3,4,5-triphosphate; C040985:phosphatidylinositol receptors; C039077:platelet protein P47; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D019204:GTP-Binding Proteins; D020823:ADP-Ribosylation Factor 1; D020727:ADP-Ribosylation Factors