Regulation of HGF-induced hepatocyte proliferation by the small GTPase Arf6 through the PIP₂-producing enzyme PIP5K1A.

ABSTRACT: HGF and its receptor c-Met are critical molecules in various biological processes. Others and we have previously shown that the small GTPase Arf6 plays a pivotal role in HGF signaling in hepatocytes. However, the molecular mechanism of how Arf6 regulates HGF signaling is unclear. Here, we show that Arf6 plays an important role in HGF-stimulated hepatocyte proliferation and liver regeneration through the phosphatidylinositol 4,5-bisphosphate (PIP₂)-producing enzyme PIP5K1A. We find that knockdown of Arf6 and PIP5K1A in HepG2 cells inhibits HGF-stimulated proliferation, Akt activation, and generation of phosphatidylinositol 3,4,5-trisphosphate (PIP₃) and its precursor PIP₂. Interestingly, PIP5K1A is recruited to c-Met upon HGF stimulation in an Arf6 activity-

SUBMITTER: Tsai MT 

PROVIDER: S-EPMC5572707 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature