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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.
F H Cruzalegui, and
M S Kapiloff, and
J P Morfin, and
B E Kemp, and
M G Rosenfeld, and
A R Means
January 1996,
Advances in pharmacology (San Diego, Calif.),
F H Cruzalegui, and
M S Kapiloff, and
J P Morfin, and
B E Kemp, and
M G Rosenfeld, and
A R Means
January 1992,
Seikagaku. The Journal of Japanese Biochemical Society,
F H Cruzalegui, and
M S Kapiloff, and
J P Morfin, and
B E Kemp, and
M G Rosenfeld, and
A R Means
November 1993,
FEBS letters,
F H Cruzalegui, and
M S Kapiloff, and
J P Morfin, and
B E Kemp, and
M G Rosenfeld, and
A R Means
December 1998,
Biochemical and biophysical research communications,
F H Cruzalegui, and
M S Kapiloff, and
J P Morfin, and
B E Kemp, and
M G Rosenfeld, and
A R Means
January 1992,
Mineral and electrolyte metabolism,
F H Cruzalegui, and
M S Kapiloff, and
J P Morfin, and
B E Kemp, and
M G Rosenfeld, and
A R Means
January 1995,
Annual review of physiology,
F H Cruzalegui, and
M S Kapiloff, and
J P Morfin, and
B E Kemp, and
M G Rosenfeld, and
A R Means
February 1989,
Trends in biochemical sciences,
F H Cruzalegui, and
M S Kapiloff, and
J P Morfin, and
B E Kemp, and
M G Rosenfeld, and
A R Means
January 1993,
Neurochemical research,
F H Cruzalegui, and
M S Kapiloff, and
J P Morfin, and
B E Kemp, and
M G Rosenfeld, and
A R Means
January 1988,
Advances in second messenger and phosphoprotein research,
F H Cruzalegui, and
M S Kapiloff, and
J P Morfin, and
B E Kemp, and
M G Rosenfeld, and
A R Means
September 2013,
Stroke,
