Phospholipase Cγ1 is a physiological guanine nucleotide exchange factor for the nuclear GTPase PIKE

Keqiang Ye, Bahman Aghdasi, Hongbo R. Luo, John L. Moriarity, Frederick Y. Wu, Jenny J. Hong, K. Joseph Hurt, Sun Sik Bae, Pann-Ghill Suh and Solomon H. Snyder ()
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Keqiang Ye: Johns Hopkins University School of Medicine, Pharmacology and Molecular Sciences and Psychiatry
Bahman Aghdasi: Johns Hopkins University School of Medicine, Pharmacology and Molecular Sciences and Psychiatry
Hongbo R. Luo: Johns Hopkins University School of Medicine, Pharmacology and Molecular Sciences and Psychiatry
John L. Moriarity: Johns Hopkins University School of Medicine, Pharmacology and Molecular Sciences and Psychiatry
Frederick Y. Wu: Johns Hopkins University School of Medicine, Pharmacology and Molecular Sciences and Psychiatry
Jenny J. Hong: Johns Hopkins University School of Medicine, Pharmacology and Molecular Sciences and Psychiatry
K. Joseph Hurt: Johns Hopkins University School of Medicine, Pharmacology and Molecular Sciences and Psychiatry
Sun Sik Bae: Pohang University of Science and Technology
Pann-Ghill Suh: Pohang University of Science and Technology
Solomon H. Snyder: Johns Hopkins University School of Medicine, Pharmacology and Molecular Sciences and Psychiatry

Nature, 2002, vol. 415, issue 6871, 541-544

Abstract: Abstract Phospholipase Cγ1 (PLC-γ1) hydrolyses phosphatidylinositol-4,5-bisphosphate to the second messengers inositol-1,4,5-trisphosphate and diacylglycerol. PLC-γ1 also has mitogenic activity upon growth-factor-dependent tyrosine phophorylation1,2; however, this activity is not dependent on the phospholipase activity of PLC-γ1, but requires an SH3 domain3,4. Here, we demonstrate that PLC-γ1 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 activity5. This enzymatic activity accounts for the mitogenic properties of PLC-γ1.

Date: 2002
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DOI: 10.1038/415541a

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