Neurochemical Research

, Volume 16, Issue 9, pp 1059–1065

Concerted regulation of protein phosphorylation and dephosphorylation by calmodulin

  • Claude B. Klee
Original Articles


The multiple functions of calmodulin in brain bring to light an apparent paradox in the mechanism of action of this multifunctional regulatory protein: How can the simultaneous calmodulin stimulation of enzymes with opposing functions such as cyclic nucleotide phosphodiesterases and adenylate cyclase, which are responsible for the degradation and synthesis of cAMP, respectively, be physiologically significant? The same question applies to the simultaneous activation of protein kinases (in particular calmodulin kinase II) and a protein phosphatase (calcineurin). One could propose that the protein kinase(s) and the phosphatase may be located in different cells or in different cellular compartments, and are therefore not antagonizing each other. The same result could be achieved if the specific substrates of these enzymes have different cellular localizations. This does not seem to be the case. In many areas of the brain the two enzymes and their substrates coexist in the same cell. For example, the hippocampus is rich in calmodulin kinase II, calcineruin and substrates for the two enzymes. A more general scheme is presented here, based on different mechanisms of the calmodulin regulation of the two classes of enzyme, which helps to solve this apparent inconsistency in the mechanism of action of calmodulin.

Key Words

Calmodulin kinase calcineurin phosphatase 


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Copyright information

© Plenum Publishing Corporation 1991

Authors and Affiliations

  • Claude B. Klee
    • 1
  1. 1.Laboratory of Biochemistry, National Cancer InstituteNational Institutes of HealthBethesda

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