SPECIFIC INTERACTION OF THE PDZ DOMAIN PROTEIN PICK1 WITH THE COOH TERMINUS OF PROTEIN-KINASE-C-ALPHA

PICK1 is a protein kinase C (PKC) alpha-binding protein initially iden tified using the yeast two-hybrid system. Here we report that PICK1 co ntains a PDZ domain that interacts specifically with a previously unid entified 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 doma in in PKC alpha is absent from other PKC isoforms that do not interact with PICK1, We also demonstrate that PICK1 can homooligomerize throug h sequences that are distinct from the carboxylate-binding loop, sugge sting that self-association and PKC alpha binding are not mutually exc lusive. A Caenorhabditis elegans PICK1-like protein is also able to bi nd to PKC alpha, suggesting a conservation of function through evoluti on. Association of PKC alpha with PICK1 provides a potential mechanism for the selective targeting of PKC alpha to unique subcellular sites.