RGS19 stimulates cell proliferation by deregulating cell cycle control and enhancing Akt signaling

RGS19 is a regulator of G protein signaling which is upregulated in ovarian cancers and its overexpression promotes cell proliferation in several mammalian cell types. Here we showed that cyclin D1/3 and Cdk6 were upregulated in HEK293 cells overexpressing RGS19, while INK4A and INK4B were reduced. Moreover, RGS19 augmented serum-stimulated PTEN/PDK/Akt and Rb phosphorylations in 293/RGS19 and Caco2/RGS19 cells. These changes were reversed upon the knockdown of RGS19. Consistent with an elevated Akt activity, increased levels of phosphorylated Bad and c-Raf and a diminished expression of TSC2 were detected, thus demonstrating that RGS19 can deregulate cell proliferation via multiple pathways.

► RGS19 as a regulator of G protein signaling. ► RGS19 upregulates the levels of cyclin D1/3 and Cdk6. ► RGS19 augments PTEN/PDK/Akt, Bad, c-Raf and Rb phosphorylations. ► RGS19 suppressed protein levels of INK4A/B and TSC2. ► RGS19 deregulates cell proliferation via multiple pathways.