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, Solomon H. Snyder

Research output: Contribution to journalArticlepeer-review

142 Scopus citations

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 phophorylation; however, this activity is not dependent on the phospholipase activity of PLC-γ1, but requires an SH3 domain. 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 activity. This enzymatic activity accounts for the mitogenic properties of PLC-γ1.

Original languageEnglish (US)
Pages (from-to)541-544
Number of pages4
JournalNature
Volume415
Issue number6871
DOIs
StatePublished - Jan 31 2002

ASJC Scopus subject areas

  • General

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