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J Biol Chem, Vol. 273, Issue 30, 19080-19085, July 24, 1998
From the Oral and Pharyngeal Cancer Branch, NIDR, National
Institutes of Health, Bethesda, Maryland 20892-4330 and the
¶ Max Planck Research Unit Molecular Cell Biology,
Medical Faculty, University of Jena, 07747 Jena, Germany
The serine/threonine protein kinase Akt has
recently been shown to be implicated in the pathway leading to cell
survival in response to serum and growth factors in a variety of
cellular systems. However, the existence of a biochemical route
connecting this kinase to the large family of receptors that signal
through heterotrimeric G proteins is yet to be explored. In this study, we set out to investigate whether GTP-binding protein (G
protein)-coupled receptors (GPCRs) can stimulate Akt activity and
survival pathways and, if so, to define the mechanism(s) whereby this
class of cell surface receptors could regulate Akt function. Using
ectopic expression of GPCRs in COS-7 cells as a model, we have observed
that both m1 and m2 muscarinic acetylcholine receptors, representative
of those GPCRs coupled to Gq and Gi
proteins, respectively, can readily activate an epitope-tagged form of
Akt kinase and prevent UV-induced apoptosis. We have also found
that the pathway connecting G proteins to Akt implicates signals
emanating from G
Activation of Akt/Protein Kinase B by G Protein-coupled
Receptors
A ROLE FOR 
AND 
SUBUNITS OF HETEROTRIMERIC G
PROTEINS ACTING THROUGH PHOSPHATIDYLINOSITOL-3-OH KINASE
q, Gi, and dimers, but not from Gs or G12, in each case
acting through a pathway that involves a phosphatidylinositol-3-OH
kinase activity. Moreover, our findings suggest a role for a novel
-sensitive complex, p101·phosphatidylinositol-3-OH kinase-,
in the transduction of signals leading to Akt stimulation and cell
survival by GPCRs and open new avenues for research on the function of
the large family of G protein-linked receptors in the regulation of
anti-apoptotic pathways.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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