Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
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Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
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Query: EC:2.7.11.17 (
CaMKII
)
4,029
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Ca2+/calmodulin-dependent protein kinases I and IV (
CaMKI
and
CaMKIV
, respectively) require phosphorylation on an equivalent single Thr in the activation loop of subdomain VIII for maximal activity. Two distinct
CaMKI
/IV kinases,
CaMKKalpha
and
CaMKKbeta
, were purified from rat brain and partially sequenced (Edelman, A. M., Mitchelhill, K., Selbert, M. A., Anderson, K. A., Hook, S. S., Stapleton, D.,
Goldstein
, E. G., Means, A. R., and Kemp, B. E. (1996) J. Biol. Chem. 271, 10806-10810). We report here the cloning and sequencing of cDNAs for human and rat
CaMKKbeta
, tissue and regional brain localization of
CaMKKbeta
protein, and mRNA and functional characterization of recombinant
CaMKKbeta
in vitro and in Jurkat T cells. The sequences of human and rat
CaMKKbeta
demonstrate 65% identity and 80% similarity with
CaMKKalpha
and 30-40% identity with
CaMKI
and
CaMKIV
themselves.
CaMKKbeta
is broadly distributed among rat tissues with highest levels in
CaMKIV
-expressing tissues such as brain, thymus, spleen, and testis. In brain,
CaMKKbeta
tracks more closely with
CaMKIV
than does
CaMKKalpha
. Bacterially expressed
CaMKKbeta
undergoes intramolecular autophosphorylation, is regulated by Ca2+/CaM, and phosphorylates
CaMKI
and
CaMKIV
on Thr177 and Thr200, respectively.
CaMKKbeta
activates both
CaMKI
and
CaMKIV
when coexpressed in Jurkat T cells as judged by phosphorylated cAMP response element-binding protein-dependent reporter gene expression.
CaMKKbeta
activity is enhanced by elevation of intracellular Ca2+, although substantial activity is observed at the resting Ca2+ concentration. The strict Ca2+ requirement of
CaMKIV
-dependent phosphorylation of cAMP response element-binding protein, is therefore controlled at the level of
CaMKIV
rather than CaMKK.
...
PMID:Components of a calmodulin-dependent protein kinase cascade. Molecular cloning, functional characterization and cellular localization of Ca2+/calmodulin-dependent protein kinase kinase beta. 982 57
