Kinase Subfamily PKA
Kinase Classification: Group AGC: Family PKA: Subfamily PKA
PKA is the canonical cAMP-regulated protein kinase subfamily with a wide variety of functions activated by GPCRs and cAMP.
Evolution
PKA is found in most or all eukaryotes. There are 3 members in mammals, alpha, beta, and gamma (PKACa, PKACb, PKACg, or PRKACa/b/g), and one in most invertebrates. Yeast has three forms, TPK1-3. Mammals have four regulatory (R) subunits, while yeast has a single one, Bcy1.
Domain Structure
Like other family members, PKA genes have a kinase domain followed by a Pkinase_C domain, though it is not always detected by hmm profile methods.
Functions
PKA forms a tetramer between two catalytic (PKAC) subunits and two regulatory (PKAR) subunits. PKA can also be anchored to many distinct subcellular locations by a large set of AKAPs (A Kinase Anchoring Proteins) [1]. Classically, binding of cAMP to regulatory subunits breaks the inactive tetramer and releases the catalytic subunit to phosphorylate a large number of substrates, depending on its localization. cAMP is generated by adenyl cyclase, usually induced by hormonal signals activating GPCRs. PKA is characterized by a large number of distinct substrates, and different pools within a cell having different and independent functions [2], unlike many kinases that are much more focused on a single function.
References
- McConnachie G, Langeberg LK, and Scott JD. AKAP signaling complexes: getting to the heart of the matter. Trends Mol Med. 2006 Jul;12(7):317-23. DOI:10.1016/j.molmed.2006.05.008 |
- Torres-Quesada O, Mayrhofer JE, and Stefan E. The many faces of compartmentalized PKA signalosomes. Cell Signal. 2017 Sep;37:1-11. DOI:10.1016/j.cellsig.2017.05.012 |
