Protein kinase A family
protein kinase a family
Protein kinase A (PKA) is composed of two regulatory (R) subunits forming a dimer, and two catalytic (C) subunits bound to the R subunits. Five different established or putative C subunit encoding genes have been identified in the human genome; PRKACA, PRKACB, PRKX, PRKY, and PRKACG. The PKA C subunit encoded by PRKACA was the first PK for which the 3D structure was solved and it has been extensively studied. Several structure-function-relationships encoded by PRKACA have proved to be conserved features of protein kinases (PKs) in general. The conserved catalytic core consists of an N-terminal lobe, called the small lobe or N-lobe, comprising mainly β-strands and a single α-helix. Located C-terminally is the large lobe or C-lobe, consisting mostly of α-helices. Between the small and large lobes is the active site cleft which binds an ATP molecule and two divalent cations. These cations are essential in the process of transferring the γ-phosphate of ATP to Ser or Thr residues on PKA substrates. The N- and C-terminal parts of PKs outside of the conserved catalytic core are termed the N- and C-tail, respectively. In the AGC subfamily of PKs, which includes PKA, the C-tail shares conserved features important for AGC kinase functioning, including a docking site for the AGC kinase activator PDK1. In contrast, the N-tail is highly variable even among the different PKA C subunits.