PKAα Catalytic Subunit [A2]

The second messenger cyclic AMP (cAMP) mediates diverse cellular responses to external signals such as proliferation, ion transport, regulation of metabolism and gene transcription by activation of the cAMP-dependent protein kinase A (cAPK or PKA). Activation of PKA occurs when cAMP binds to the two regulatory subunits of the tetrameric PKA holoenzyme, resulting in release of active catalytic subunits. Three catalytic (C) subunits have been identified, designated PKAα cat (Cα), PKAβ cat (Cβ) and PKAγ cat (Cγ). Each subunit represents specific gene products. PKAα cat and PKAβ cat are closely related (93% amino acid sequence similarity), whereas PKAγ cat displays 83% and 79% similarity to PKAα cat and PKAβ cat, respectively. Activation of transcription upon elevation of cAMP levels results from translocation of PKA to the nucleus where it phosphorylates the transcription factor cAMP response element binding protein (CREB) on Serine 133, which in turn leads to TFIIB binding to TATA-box-binding protein TBP1, thus linking phospho-CREB to the Pol II transcription initiation complex.