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.
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We thank G. Carpenter and G. Shawn for some of the plasmids. This work is supported by United States Public Health Service grants (S.H.S.), and Research Scientist Award (S.H.S.).
The authors declare no competing financial interests.
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Ye, K., Aghdasi, B., Luo, H. et al. Phospholipase Cγ1 is a physiological guanine nucleotide exchange factor for the nuclear GTPase PIKE. Nature 415, 541–544 (2002). https://doi.org/10.1038/415541a
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