Phospholipase Cγ1 is a physiological guanine nucleotide exchange factor for the nuclear GTPase PIKE
Copyright policy )Phospholipase Cγ1 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.
- Johns Hopkins Medicine United States
- Johns Hopkins University School of Medicine United States
- UNIST (Ulsan National Institute of Science and Technology) Korea (Republic of)
- Pohang University of Science and Technology Korea (Republic of)
STRUCTURAL BASIS, Recombinant Fusion Proteins, PC12 Cells, ACTIVATION, src Homology Domains, Phosphatidylinositol 3-Kinases, GTP-Binding Proteins, Animals, Guanine Nucleotide Exchange Factors, SH3 DOMAINS, PROTEIN 4.1N, Monomeric GTP-Binding Proteins, CELL-DIFFERENTIATION, FRIEND-CELLS, Phospholipase C gamma, NERVE GROWTH-FACTOR, Rats, C-GAMMA, Enzyme Activation, Isoenzymes, Type C Phospholipases, ras Proteins, PC12 CELLS, Mitogens, RAS, Protein Binding
STRUCTURAL BASIS, Recombinant Fusion Proteins, PC12 Cells, ACTIVATION, src Homology Domains, Phosphatidylinositol 3-Kinases, GTP-Binding Proteins, Animals, Guanine Nucleotide Exchange Factors, SH3 DOMAINS, PROTEIN 4.1N, Monomeric GTP-Binding Proteins, CELL-DIFFERENTIATION, FRIEND-CELLS, Phospholipase C gamma, NERVE GROWTH-FACTOR, Rats, C-GAMMA, Enzyme Activation, Isoenzymes, Type C Phospholipases, ras Proteins, PC12 CELLS, Mitogens, RAS, Protein Binding
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