Editors' ChoiceCell proliferation

PLC-γ1 "sPIKES" PI3K Activity

Science's STKE  05 Feb 2002:
Vol. 2002, Issue 118, pp. tw53
DOI: 10.1126/stke.2002.118.tw53

The phosphatidylinositol 3-kinase (PI3K) enhancer (PIKE) is small guanosine triphosphatase (GTPase) that associates with nuclear-localized PI3K and increases its lipid kinase activity and its ability to promote cellular proliferation. Activated phospholipase C-γ1 (PLC-γ1) can also promote mitogenesis, but this effect does not require the phospholipase activity of PLC-γ1. Now Ye et al. have found that PLC-γ1 might act as a guanine nucleotide exchange factor (GEF) for PIKE. The Src homology 3 (SH3) domain of PLC-γ1 (PLCγ1-SH3) bound to PIKE in glutathione S-transferase pull-down assays. Increasing concentrations of the PLCγ1-SH3 incubated with PIKE stimulated GTP binding to and GDP dissociation from PIKE. These data suggest that PLCγ1-SH3 functioned like a GEF with PIKE as its substrate. PC12 cells that expressed PLCγ1-SH3 exhibited increased nuclear PI3K activity, suggesting a link between PLC-γ1 and increased PI3K activity, and a possible explanation of how PLC-γ1 can promote phospholipase-independent cell proliferation.

K. Ye, B. Aghdasi, H. R. Luo, J. L. Moriarity, F. Y. Wu, J. J. Hong, K. J. Hurt, S. S. Bae, P.-G. Suh, S. H. Snyder, Phospholipase Cγ1 is a physiological guanine nucleotide exchange factor for the nuclear GTPase PIKE. Nature 415, 541-544 (2002). [Online Journal]