Regulation of intrasteric inhibition of the multifunctional calcium/calmodulin-dependent protein kinase.

Journal Article (Journal Article)

A regulatory region involved in both autoinhibition and calmodulin (CaM) binding has previously been identified in the multifunctional Ca2+/CaM-dependent protein kinase (CaM kinase II). We have tested the role of various segments of the regulatory region in autoinhibition by the analysis of a series of truncation, substitution, and deletion mutants of the CaM kinase II alpha subunit (CaM kinase II alpha). Unexpectedly, the sequence Lys-Lys-Phe-Asn at positions 291-294, adjacent to the CaM binding domain, was found to be sufficient to maintain an inhibited state in a truncated form of the kinase. However, these residues are not essential in the context of the full-length protein, indicating the importance of additional residues from the overlapping CaM binding domain. We propose here a molecular model for CaM kinase II alpha based on the three-dimensional structure of the cAPK-PKI-(5-24) (protein kinase inhibitor fragment) complex. It is predicted from this model that autoinhibition is of the pseudosubstrate variety and that autophosphorylation of Thr-286 could occur by an intersubunit reaction in the holoenzyme complex.

Full Text

Duke Authors

Cited Authors

  • Cruzalegui, FH; Kapiloff, MS; Morfin, JP; Kemp, BE; Rosenfeld, MG; Means, AR

Published Date

  • December 15, 1992

Published In

Volume / Issue

  • 89 / 24

Start / End Page

  • 12127 - 12131

PubMed ID

  • 1334558

Pubmed Central ID

  • PMC50711

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.89.24.12127


  • eng

Conference Location

  • United States