Phospholipase C–γ1: A Phospholipase and Guanine Nucleotide Exchange Factor

Abstract

Although phospholipase C-γ (PLC-γ) participates in cellular mitogenesis, evidence indicates that the catalytic activity of PLC-γ (to hydrolyze certain phosphoinositides) is nonessential to the process. So how is it that PLC-γ is necessary but its lipase activity is not? Recently published results from Snyder and colleagues describe the ability of PLC-γ to facilitate guanine nucleotide exchange for the recently identified nucleus-localized GTPase PIKE, which acts to enhance the enzymatic activity of phosphatidylinositol 3′-kinase (PI3K). The authors contend that the SH3 domain, rather than the catalytic domain, of PLC-γ is required for aiding PIKE, and furthermore, that the mitogenic activity of PLC-γ depends not on its phospholipase activity, but rather on its interaction with PIKE. Wang and Moran examine the results and piece together a picture of how PLC-γ cooperates with PIKE.