PIKE GTPase: a novel mediator of phosphoinositide signaling.
Phosphoinositide (PI) 3-kinase enhancer (PIKE) is a brain-specific GTPase that binds to PI 3-kinase and stimulates its lipid kinase activity. It exists in two forms: the first to be identified, PIKE-S, is shorter and exclusively nuclear; by contrast, the longer form, PIKE-L, resides in multiple intracellular compartments. Nerve growth factor treatment leads to PIKE-S activation by triggering the nuclear translocation of phospholipase C (PLC)-gamma 1, which acts as a physiological guanine nucleotide exchange factor (GEF) for PIKE-S through its Src-homology 3 (SH3) domain. Cytoplasmic PI 3-kinase and its lipid product phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P3] regulate the membrane translocation and activation of many signaling molecules by binding to their pleckstrin homology (PH) domains. However, little is known about the physiological roles of their nuclear counterparts. The nuclear PLC-gamma 1/PIKE-S/PI 3-kinase signaling pathway seems to be an extension of the crosstalk between cytoplasmic PLC-gamma 1 and PI 3-kinase. PIKE-L contains a C-terminal extension consisting of an ADP ribosylation-GTPase-activating protein (ArfGAP) domain and two ankyrin repeats in addition to the N-terminal GTPase domain. PIKE-L could have additional, extranuclear functions, including regulation of postsynaptic signaling by metabotropic glutamate receptors.
Ye
Keqiang
K
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USA. kye@emory.edu
Snyder
Solomon H
SH
D001921:Brain / Q000201:enzymology; D002467:Cell Nucleus / Q000378:metabolism; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D050356:Lipid Metabolism; D020559:Monomeric GTP-Binding Proteins; D020932:Nerve Growth Factor / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D051966:Phospholipase C gamma; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017470:Receptors, Glutamate / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism*
D020662:Guanine Nucleotide Exchange Factors; D007527:Isoenzymes; D010716:Phosphatidylinositols; D017470:Receptors, Glutamate; D020932:Nerve Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; C418731:Agap2 protein, rat; D019204:GTP-Binding Proteins; D020559:Monomeric GTP-Binding Proteins; D018631:ras Proteins