Identification of the Major Postsynaptic Density Protein as Homologous with the Major Calmodulin-Binding Subunit of a Calmodulin-Dependent Protein Kinase


Address correspondence and reprint requests to Robert J. DeLorenzo, Department of Neurology, Yale University School of Medicine. 333 Cedar St., New Haven. CT 06510. U.S.A.


Abstract: The major postsynaptic density protein (mPSDp), comprising >50% of postsynaptic density (PSD) protein, is an endogenous substrate for calmodulin-dependent phosphorylation as well as a calmodulin-binding protein in PSD preparations. The results in this investigation indicate that mPSDp is highly homologous with the major calmodulin-binding subunit (p) of tubulin-associated calmodulin-dependent kinase (TACK), and that PSD fractions also contain a protein homologous with the o-subunit of TACK. Homologies between mPSDp and a 63,000 dalton PSD protein and the p- and ó-subunits of TACK were established by the following criteria: (1) identical apparent molecular weights: (2) identical calmodulin-binding properties; (3) manifestation of Ca2+ -calmodulin-stimulated autophosphorylation; (4)identical isoelectric points; (5) identical calmodulin binding and autophosphorylation patterns on two-dimensional gels; (6) homologous two-dimensional tryptic peptide maps; and (7) similar phosphoamino acid-specific phosphorylation of tubulin. The results suggest that mPSDp is a calmodulin-binding protein involved in modulating protein kinase activity in the postsynaptic density and that a tubulin kinase system homologous with TACK exists in a membrane-bound form in the PSD.