Phospholipase C gamma 1 is a physiological guanine nucleotide exchange factor for the nuclear GTPase PIKE.
Phospholipase C gamma 1 (PLC-gamma 1) hydrolyses phosphatidylinositol-4,5-bisphosphate to the second messengers inositol-1,4,5-trisphosphate and diacylglycerol. PLC-gamma 1 also has mitogenic activity upon growth-factor-dependent tyrosine phosphorylation; however, this activity is not dependent on the phospholipase activity of PLC-gamma 1, but requires an SH3 domain. Here, we demonstrate that PLC-gamma 1 acts as a guanine nucleotide exchange factor (GEF) for PIKE (phosphatidylinositol-3-OH kinase (PI(3)K) enhancer). PIKE is a nuclear GTPase that activates nuclear PI(3)K activity, and mediates the physiological activation by nerve growth factor (NGF) of nuclear PI(3)K activity. This enzymatic activity accounts for the mitogenic properties of PLC-gamma 1.
Ye
Keqiang
K
Johns Hopkins University School of Medicine, Department of Neuroscience, 725 N. Wolfe Street, Baltimore, Maryland 21205, USA.
Aghdasi
Bahman
B
Luo
Hongbo R
HR
Moriarity
John L
JL
Wu
Frederick Y
FY
Hong
Jenny J
JJ
Hurt
K Joseph
KJ
Bae
Sun Sik
SS
Suh
Pann-Ghill
PG
Snyder
Solomon H
SH
D000818:Animals; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000502:physiology*; D007527:Isoenzymes / Q000502:physiology*; D008934:Mitogens / Q000502:physiology; D020559:Monomeric GTP-Binding Proteins; D016716:PC12 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051966:Phospholipase C gamma; D011485:Protein Binding; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D010738:Type C Phospholipases / Q000502:physiology*; D018631:ras Proteins / Q000378:metabolism*; D018909:src Homology Domains
D020662:Guanine Nucleotide Exchange Factors; D007527:Isoenzymes; D008934:Mitogens; D011993:Recombinant Fusion Proteins; 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