|
|
||||||||
s in vivo
1 Department of Molecular Pharmacology and 2 Department of Physiology and Biophysics, Diabetes and Metabolic Diseases Research Program, University Medical Center, State University of New York at Stony Brook, Stony Brook, New York 11794
We report
the creation of transgenic mice with an inducible, tissue-targeted
expression of a constitutively active mutant form (Q227L) of
G
s. Mice expressing activated G
s in fat
tissue, liver, and skeletal muscle displayed normal body mass and
blunted glucose metabolism. cAMP accumulation in adipose tissue was
increased in the basal state, but far less than would be expected.
Marked adaptation to elevated cAMP levels occurred, leading to an
increase in total cAMP-specific phosphodiesterase activity, a 50%
decline in cAMP-dependent protein kinase (protein kinase A) activity, and an increased expression of G
i2. The reduction in
kinase activity coincided with >50% increase in the expression of
RI
and RII
regulatory subunits of protein kinase A, with no
change in the amount of catalytic subunit. These data demonstrate the
existence of adaptive responses of protein kinase A, phosphodiesterase, and G
i2 in tissues expressing constitutively active
G
s that may act to rectify the impact of increased cAMP accumulation.
constitutively activated G
s; protein kinase A; regulatory subunits
This article has been cited by other articles:
![]() |
N. Wettschureck and S. Offermanns Mammalian G Proteins and Their Cell Type Specific Functions Physiol Rev, October 1, 2005; 85(4): 1159 - 1204. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. F. Steinberg Focus on "Targeted expression of activated Q227L Galpha s in vivo" Am J Physiol Cell Physiol, August 1, 2002; 283(2): C383 - C385. [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |