Differential Binding of cAMP-dependent Protein Kinase Regulatory Subunit Isoforms Iα and IIβ to the Catalytic Subunit

摘要: Limited trypsin digestion of type I cAMP-dependent protein kinase holoenzyme results in a proteolytic-resistant Δ(1–72) regulatory subunit core, indicating that interaction between the and catalytic subunits extends beyond autoinhibitory site R at NH2 terminus. Sequence alignment two isoforms, RI RII, reveals significantly sequence diversity this specific region. To determine whether is functionally important for with subunit, mutations, R133A D328A, are introduced into sites adjacent to active cleft subunit. While replacing Arg133 Ala decreases binding affinity not affected. In contrast, mutant C(D328A) showed decrease while maintaining similar affinities RII as compared wild-type These suggest immediately NH2-terminal consensus inhibition interacts different proximal region isoform-specific differences would dictate domain organization II holoenzymes.