Specific interaction of the PDZ domain protein PICK1 with the COOH terminus of protein kinase C-α

PICK1 is a protein kinase C (PKC) alpha-binding protein initially identified using the yeast two-hybrid system. Here we report that PICK1 contains a PDZ domain that interacts specifically with a previously unidentified PDZ-binding domain (QSAV) at the extreme COOH terminus of PKC alpha and that mutation of a putative carboxylate-binding loop within the PICK1 PDZ domain abolishes this interaction. The PDZ binding domain in PKC alpha is absent from other PKC isoforms that do not interact with PICK1, We also demonstrate that PICK1 can homooligomerize through sequences that are distinct from the carboxylate-binding loop, suggesting that self-association and PKC alpha binding are not mutually exclusive. A Caenorhabditis elegans PICK1-like protein is also able to bind to PKC alpha, suggesting a conservation of function through evolution. Association of PKC alpha with PICK1 provides a potential mechanism for the selective targeting of PKC alpha to unique subcellular sites.