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

Authors

  • James R. Goldenring,

    1. Departments of Neurology and Dermatology, Yale University School of Medicine, New Haven, Connecticut, U.S.A.
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  • Joseph S. McGuire Jr.,

    1. Departments of Neurology and Dermatology, Yale University School of Medicine, New Haven, Connecticut, U.S.A.
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  • Robert J. DeLorenzo

    Corresponding author
    1. Departments of Neurology and Dermatology, Yale University School of Medicine, New Haven, Connecticut, U.S.A.
      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.
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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

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.

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