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

Author

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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)

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.

Suggested Citation

  • 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, 2002. "Phospholipase Cγ1 is a physiological guanine nucleotide exchange factor for the nuclear GTPase PIKE," Nature, Nature, vol. 415(6871), pages 541-544, January.
    • Handle: RePEc:nat:nature:v:415:y:2002:i:6871:d:10.1038_415541a
    DOI: 10.1038/415541a
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