AN AUTOREGULATORY REGION IN PROTEIN-KINASE-C - THE PSEUDOANCHORING SITE

We have previously identified receptors for activated C kinase (RACKs) as components of protein kinase C (PKC) signaling, RACK1, a recently cloned 36-kDa RACK, has short sequences of homology to PKC, A possible explanation for the homologous sequences between the ligand (PKC) and its intracellular receptor (RACK1) may be that, similar to the pseudo substrate autoregulatory sequence on PKC, there is also a pseudo RACK1 binding site on the enzyme, If this is the case, peptides with these sequences (derived from either RACK1 or PKC) are expected to affect PK C binding to RACK1 in vitro and PKC-mediated functions in vivo, Here, we show that the PKC-derived peptide (pseudo-RACK1 peptide), but not i ts RACK1 homologue, modulated PKC function both in vitro and in vivo, Our data suggest that the pseudo-RACK1 peptide binds and activates PKC in the absence of PKC activators and thereby acts as an agonist of PK C function in vivo. Therefore, the pseudo-RACK1 sequence in PKC appear s to be another autoregulatory site; when PKC is in an inactive confor mation, the pseudo-RACK1 site interacts with the RACK-binding site, Ac tivation of PKC exposes the RACK-binding site, enabling the associatio n of the enzyme with its anchoring RACK, Similar pseudoanchoring sites may regulate the function of other protein kinases.