Phospholipase C-γ1 (PLC-γ1) is a critical signalling molecule in the regulation of cell proliferation. Its downstream effects depend both on its lipase activity – through which it generates inositol 1,4,5-trisphosphate and diacylglycerol – and on its SH2 and SH3 domains. Now, Pann-Ghill Suh and co-workers report that PLC-γ1 is also a guanine nucleotide exchange factor (GEF) that regulates the GTPase dynamin 1 and suggest that it is involved in the regulation of endocytosis (see p. 3785). Dynamin 1 drives clathrin-mediated endocytosis of numerous proteins, including growth factor receptors. In their paper, the authors show that PLC-γ1 functions as a dynamin 1 GEF in vitro and in vivo through a direct interaction between its SH3 domain and the GTPase. Overexpression of PLC-γ1 in PC12 cells enhances dynamin-1-dependent endocytosis of epidermal growth factor (EGF) receptor and as a result stimulates activation of the MAP kinase ERK, which is downstream of the EGF receptor. By contrast, downregulation of PLC-γ1 by siRNA reduces ERK activation. Suh and co-workers propose that PLC-γ1 functions as a key molecule in growth-factor-induced proliferation by regulating growth factor endocytosis.