Peeters Tom, Versele Matthias, Thevelein Johan M
Laboratory of Molecular Cell Biology, Institute of Botany and Microbiology, Katholieke Universiteit Leuven, Flanders Interuniversity Institute for Biotechnology (VIB), Leuven-Heverlee, Flanders, Belgium.
Trends Biochem Sci. 2007 Dec;32(12):547-54. doi: 10.1016/j.tibs.2007.09.011. Epub 2007 Nov 5.
One major class of G proteins typically functions as heterotrimeric complexes consisting of Galpha, Gbeta and Ggamma subunits. However, recent work in yeast has identified an atypical Galpha protein, Gpa2p, which functions without cognate Gbetagamma subunits. Two novel kelch repeat protein binding partners of Gpa2p, Krh1p and Krh2p, do not function as alternative Gbeta 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 Galpha proteins could exhibit similar characteristics to Gpa2p.
一类主要的G蛋白通常作为由α-、β-和γ-亚基组成的异源三聚体复合物发挥作用。然而，最近在酵母中的研究发现了一种非典型的α-蛋白Gpa2p，它在没有同源βγ-亚基的情况下发挥作用。Gpa2p的两个新的kelch重复蛋白结合伙伴Krh1p和Krh2p，并不像最初认为的那样作为替代的β-亚基发挥作用，而是作为Gpa2p的效应器。它们直接将Gpa2p与蛋白激酶A联系起来，从而形成一条腺苷酸环化酶旁路途径，使除细胞cAMP浓度以外的输入能够影响蛋白激酶A的活性。由于在酵母中表达的哺乳动物蛋白激酶A也受同一旁路途径的控制，因此推测在哺乳动物细胞中可能存在功能类似的机制，并且其他α-蛋白可能具有与Gpa2p相似的特征，这是令人兴奋的。
