CAMP activation of PKA defines an ancient signaling mechanism.

ABSTRACT: cAMP and the cAMP binding domain (CBD) constitute a ubiquitous regulatory switch that translates an extracellular signal into a biological response. The CBD contains alpha- and beta-subdomains with cAMP binding to a phosphate binding cassette (PBC) in the beta-sandwich. The major receptors for cAMP in mammalian cells are the regulatory subunits (R-subunits) of PKA where cAMP and the catalytic subunit compete for the same CBD. The R-subunits inhibit kinase activity, whereas cAMP releases that inhibition. Here, we use NMR to map at residue resolution the cAMP-dependent interaction network of the CBD-A domain of isoform Ialpha of the R-subunit of PKA. Based on H/D, H/H, and N(z) exchange data, we propose a molecular model for the allosteric regulation of PKA by cAMP. According to our model, c

SUBMITTER: Das R 

PROVIDER: S-EPMC1765484 | biostudies-literature | 2007 Jan

REPOSITORIES: biostudies-literature