Gα16 interacts with Class IA phosphatidylinositol 3-kinases and inhibits Akt signaling

Abstract Phosphatidylinositol 3-kinase (PI3K) mediates receptor tyrosine kinase and G protein coupled receptor (GPCR) signaling by phosphorylating phosphoinositides to elicit various biological responses. Gα q has previously been shown to inhibit class IA PI3K by interacting with the p110α subunit. However, it is not known if PI3Ks can associate with other Gα q family members such as Gα 16 . Here, we demonstrated that class IA PI3Ks, p85/p110α and p85/p110β, could form stable complexes with wild type Gα 16 and its constitutively active mutant (Gα 16 QL) in HEK293 cells. In contrast, no interaction between Gα 16 and class IB PI3K was observed. The Gα 16 /p110α signaling complex could be detected in hematopoietic cells that endogenously express Gα 16 . Overexpression of class I PI3Ks did not inhibit Gα 16 QL-induced IP 3 production and, unlike p63RhoGEF, class IA PI3Ks did not attenuate the binding of PLCβ 2 to Gα 16 QL. On the contrary, the function of class IA PI3Ks was suppressed by Gα 16 QL as revealed by diminished production of PIP 3 as well as inhibition of EGF-induced Akt phosphorylation. Taken together, these results suggest that Gα 16 can bind to class IA PI3Ks and inhibit the PI3K signaling pathway.