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Sci. STKE, 19 December 2006
Vol. 2006, Issue 366, p. tw425
[DOI: 10.1126/stke.3662006tw425]

EDITORS' CHOICE

G Proteins The "Other" G Protein Corrals PKA

Elizabeth M. Adler

Science’s 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 {alpha}-subunits on adenylyl cyclase, the known effects of Go--the most abundant brain G protein--are mostly mediated by the Gbeta{gamma} dimer, with specific functions of G{alpha}o remaining unclear. Noting that evidence exists both for direct effects of G{alpha}o 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 G{alpha}o and PKA regulatory and catalytic subunits (RIIbeta and C{alpha}) indicated that G{alpha}o bound PKA catalytic subunits. G{alpha}i did not bind C{alpha}, and analysis of G{alpha}i-G{alpha}o chimeras indicated that G{alpha}o bound PKA through its GTPase domain. G{alpha}o did not inhibit the catalytic activity of purified C{alpha}; however, immunocytochemical analysis of COS7 cells transfected with FLAG-tagged G{alpha} constructs and stimulated with forskolin indicated that the G{alpha}o-C{alpha} interaction inhibited translocation of C{alpha} to the nucleus. Moreover, pharmacological analysis of GH4C1 rat pituitary tumor cells (containing endogenous Go and PKA) indicated that Go inhibited not only C{alpha} translocation to the nucleus but also PKA-dependent cAMP response element-binding protein (CREB) phosphorylation. In contrast, G{alpha}o spared--or even facilitated--the cytosolic effects of PKA. Thus, the authors propose that, by binding C{alpha}, G{alpha}o 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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