Sci. STKE, 19 December 2006
G Proteins The "Other" G Protein Corrals PKA
Elizabeth M. Adler
Sciences STKE, AAAS, Washington, DC 20005, USA
Whereas Gs- and Gi-type heterotrimeric GTP-binding proteins (G proteins) are well known for the stimulatory and inhibitory effects of their -subunits on adenylyl cyclase, the known effects of Go--the most abundant brain G protein--are mostly mediated by the G dimer, with specific functions of Go remaining unclear. Noting that evidence exists both for direct effects of Go and for crosstalk between Go and cAMP-dependent protein kinase (PKA) signaling, Ghil et al. looked for possible interactions between Go and PKA. Both in vitro analysis and immunoprecipitation of 293T cells overexpressing Go and PKA regulatory and catalytic subunits (RII and C) indicated that Go bound PKA catalytic subunits. Gi did not bind C, and analysis of Gi-Go chimeras indicated that Go bound PKA through its GTPase domain. Go did not inhibit the catalytic activity of purified C; however, immunocytochemical analysis of COS7 cells transfected with FLAG-tagged G constructs and stimulated with forskolin indicated that the Go-C interaction inhibited translocation of C to the nucleus. Moreover, pharmacological analysis of GH4C1 rat pituitary tumor cells (containing endogenous Go and PKA) indicated that Go inhibited not only C translocation to the nucleus but also PKA-dependent cAMP response element-binding protein (CREB) phosphorylation. In contrast, Go spared--or even facilitated--the cytosolic effects of PKA. Thus, the authors propose that, by binding C, Go directs its subcellular localization and thereby regulates its downstream effects.
S. Ghil, J.-M. Choi, S.-S. Kim, Y.-D. Lee, Y. Liao, L. Birnbaumer, H. Suh-Kim, Compartmentalization of protein kinase A signaling by the heterotrimeric G protein Go. Proc. Natl. Acad. Sci. U.S.A. 103, 19158-19163 (2006). [Abstract] [Full Text]
Citation: E. M. Adler, The "Other" G Protein Corrals PKA. Sci. STKE 2006, tw425 (2006).
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