RGD Reference Report - Differential regulatory mechanism of Ca2+/calmodulin-dependent protein kinase kinase isoforms. - Rat Genome Database

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Differential regulatory mechanism of Ca2+/calmodulin-dependent protein kinase kinase isoforms.

Authors: Tokumitsu, H  Iwabu, M  Ishikawa, Y  Kobayashi, R 
Citation: Tokumitsu H, etal., Biochemistry 2001 Nov 20;40(46):13925-32.
RGD ID: 632490
Pubmed: PMID:11705382   (View Abstract at PubMed)

We have previously demonstrated that the alpha isoform of Ca(2+)/calmodulin-dependent protein kinase kinase (CaM-KKalpha) is strictly regulated by an autoinhibitory mechanism and activated by the binding of Ca(2+)/CaM [Tokumitsu, H., Muramatsu, M., Ikura, M., and Kobayashi, R. (2000) J. Biol. Chem. 275, 20090-20095]. In this study, we find that rat brain extract contains Ca(2+)/CaM-independent CaM-KK activity. This result is consistent with an enhanced Ca(2+)/CaM-independent activity (60-70% of total activity) observed with the recombinant CaM-KKbeta isoform. By using various truncation mutants of CaM-KKbeta, we have identified a region of 23 amino acids (residues 129-151) located at the N-terminus of the catalytic domain as an important regulatory element of the autonomous activity. A CaM-KKbeta deletion mutant of this domain shows a significant increase of Ca(2+)/CaM dependency for the CaM-KK activity as well as for the autophosphorylation activity. The activities of CaM-KKalpha and CaM-KKbeta chimera, in which autoinhibitory sequences were replaced by each other, were completely dependent on Ca(2+)/CaM, suggesting that the autoinhibitory regions of CaM-KKalpha and CaM-KKbeta are functional. These results establish for the first time that residues 129-151 of CaM-KKbeta participate in the release of the autoinhibitory domain from its catalytic core, resulting in generation of autonomous activity.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein phosphorylation  TAS 632490 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
calmodulin-dependent protein kinase activity  TAS 632490 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Camkk1  (calcium/calmodulin-dependent protein kinase kinase 1)

Objects referenced in this article
Gene Pnck pregnancy up-regulated nonubiquitous CaM kinase Rattus norvegicus

Additional Information