dimerization/docking (D/D) domain of the type II Regulatory subunit of cAMP-dependent protein kinase and similar domains
cAMP-dependent protein kinase (PKA) is a serine/threonine kinase (STK), catalyzing the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. There are two classes of R subunits, RI and RII; each exists as two isoforms (alpha and beta) from distinct genes. These functionally non-redundant R isoforms allow for specificity in PKA signaling. The R subunit contains an N-terminal dimerization/docking (D/D) domain, a linker with an inhibitory sequence (IS), and two c-AMP binding domains. RI and RII subunits are distinguished by their IS; RII subunits contain a phosphorylation site and are both substrates and inhibitors while RI subunits are pseudo-substrates. RI subunits require ATP and Mg ions to form a stable holoenzyme while RII subunits do not. The D/D domain dimerizes to form a four-helix bundle that serves as a docking site for A-kinase-anchoring proteins (AKAPs), which facilitates the localization of PKA to specific sites in the cell. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis.
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