Regulation of Ca2+/calmodulin-dependent protein kinase II by Ca2+/calmodulin-independent autophosphorylation

R. Lickteig, S. Shenolikar, Larry Denner, P. T. Kelly

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The autophosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaM-KII) results in the generation of kinase activity that is largely Ca2+/CaM-independent. We report that continued Ca2+/CaM-independent autophosphorylation of CaM-KII results in the generation of distinct phosphopeptides as identified by high performance liquid chromatography and enzymatic properties that are different than those observed for Ca2+/CaM-dependent autophosphorylation. These Ca2+/CaM-independent properties include (a) increased catalytic activity, (b) higher substrate affinity for the phorphorylation of synapsin I, and (c) decreased CaM-binding to both CaM-KII subunits as analyzed by gel overlays. Our results indicate that the autophosphorylation of only one subunit per holoenzyme is required to generate the Ca2+/CaM-independent CaM-KII. We suggest a two-step process by which autophosphorylation regulates CaM-KII. Step I requires Ca2+/CaM and underlies initial kinase activation. Step II involves continued autophosphorylation of the Ca2+/CaM-independent kinase and results in increased affinity for its substrate synapsin I and decreased affinity for calmodulin. These results indicate a complex mechanism through which autophosphorylation of CaM-KII may regulate its activity in response to transient fluctuations in intracellular calcium.

Original languageEnglish (US)
Pages (from-to)19232-19239
Number of pages8
JournalJournal of Biological Chemistry
Volume263
Issue number35
StatePublished - 1988
Externally publishedYes

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Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calmodulin
Synapsins
Phosphotransferases
Phosphopeptides
Holoenzymes
High performance liquid chromatography
Substrates
Catalyst activity
Gels
Chemical activation
High Pressure Liquid Chromatography
Calcium

ASJC Scopus subject areas

  • Biochemistry

Cite this

Regulation of Ca2+/calmodulin-dependent protein kinase II by Ca2+/calmodulin-independent autophosphorylation. / Lickteig, R.; Shenolikar, S.; Denner, Larry; Kelly, P. T.

In: Journal of Biological Chemistry, Vol. 263, No. 35, 1988, p. 19232-19239.

Research output: Contribution to journalArticle

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