Journal
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
Volume 1784, Issue 1, Pages 16-26Publisher
ELSEVIER
DOI: 10.1016/j.bbapap.2007.10.002
Keywords
PKA; PKI; holoenzyme; RI alpha; RII alpha; signaling; allostery; dynamic; kinase inhibitor; a kinase anchoring proteins (AKAPs)
Categories
Funding
- NCI NIH HHS [CA 09523, T32 CA009523] Funding Source: Medline
- NIDDK NIH HHS [P01 DK054441, DK 54441, P01 DK054441-09] Funding Source: Medline
- NIGMS NIH HHS [R01 GM034921, R37 GM019301, GM 19301, R01 GM034921-22, T32 GM008326, R01 GM019301-36, R01 GM019301, GM 34921, GM 08326] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [T32CA009523] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P01DK054441] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R37GM019301, R01GM019301, T32GM008326, R01GM034921] Funding Source: NIH RePORTER
Ask authors/readers for more resources
The catalytic subunit of cAMP-dependent protein kinase has served as a prototype for the protein kinase superfamily for many years while structures of the cAMP-bound regulatory subunits have defined the conserved cyclic nucleotide binding (CNB) motif. It is only structures of the holoenzymes, however, that enable us to appreciate the molecular features of inhibition by the regulatory subunits as well as activation by cAMP. These structures reveal for the first time the remarkable malleability of the regulatory subunits and the CNB domains. At the same time, they allow us to appreciate that the catalytic subunit is not only a catalyst but also a scaffold that mediates a wide variety of protein:protein interactions. The holoenzyme structures also provide a new paradigm for designing isoform-specific activators and inhibitors of PKA. In addition to binding to the catalytic subunits, the regulatory subunits also use their N-terminal dimerization/docking domain to bind with high affinity to A Kinase Anchoring Proteins using an amphipathic helical motif. This targeting mechanism, which localizes PKA near to its protein substrates, is also a target for therapeutic intervention of PKA signaling. (C) 2007 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available