P90 ribosomal S6 kinase 1 (RSK1) and the catalytic subunit of protein kinase A (PKA) compete for binding the pseudosubstrate region of PKAR1alpha: role in the regulation of PKA and RSK1 activities.

ABSTRACT: Previously we showed that the inactive form of p90 ribosomal S6 kinase 1 (RSK1) interacts with the regulatory subunit, PKARIalpha, of protein kinase A (PKA), whereas the active RSK1 interacts with the catalytic subunit (PKAc) of PKA. Herein, we demonstrate that the N-terminal kinase domain (NTK) of RSK1 is necessary for interactions with PKARIalpha. Substitution of the activation loop phosphorylation site (Ser-221) in the NTK with the negatively charged Asp residue abrogated the association between RSK1 and PKARIalpha. This explains the lack of an interaction between active RSK1 and PKARIalpha. Full-length RSK1 bound to PKARIalpha with an affinity of 0.8 nm. The NTK domain of RSK1 competed with PKAc for binding to the pseudosubstrate region (amino acids 93-99) of PKARIalpha. Overexpressed

SUBMITTER: Gao X 

PROVIDER: S-EPMC2844146 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature