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 C(alpha), C(beta) and C(gamma), that each represent specific gene products. C(alpha) and C(beta) are closely related (93% amino acid sequence similarity), whereas C(gamma) displays 83% and 79% similarity to C(alpha) and C(beta), 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.