Distal recognition sites in substrates are required for efficient phosphorylation by the cAMP-dependent protein kinase.

ABSTRACT: Protein kinases are important mediators of signal transduction in eukaryotic cells, and identifying the substrates of these enzymes is essential for a complete understanding of most signaling networks. In this report, novel substrate-binding variants of the cAMP-dependent protein kinase (PKA) were used to identify substrate domains required for efficient phosphorylation in vivo. Most wild-type protein kinases, including PKA, interact only transiently with their substrates. The substrate domains identified were distal to the sites of phosphorylation and were found to interact with a C-terminal region of PKA that was itself removed from the active site. Only a small set of PKA alterations resulted in a stable association with substrates, and the identified residues were clustered together wi

SUBMITTER: Deminoff SJ 

PROVIDER: S-EPMC2691761 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature