Directly from Gα to protein kinase A: the kelch repeat protein bypass of adenylate cyclase

One major class of G proteins typically functions as heterotrimeric complexes consisting of Gα, Gβ and Gγ subunits. However, recent work in yeast has identified an atypical Gα protein, Gpa2p, which functions without cognate Gβγ subunits. Two novel kelch repeat protein binding partners of Gpa2p, Krh1p and Krh2p, do not function as alternative Gβ subunits, as initially thought, but rather as Gpa2p effectors. They directly link Gpa2p to protein kinase A, thus forming an adenylate cyclase bypass pathway that enables inputs other than cellular cAMP concentration to affect protein kinase A activity. Because mammalian protein kinase A expressed in yeast is also subject to control by the same bypass pathway, it is exciting to postulate that a functionally similar mechanism might exist in mammalian cells, and that other Gα proteins could exhibit similar characteristics to Gpa2p.