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Modulation of the Phosphorylation and Activity of Calcium/Calmodulin‐Dependent Protein Kinase II by Zinc
Author(s) -
Lengyel Imre,
FieuwMakaroff Sabine,
Hall Amanda L,
Sim Alistair T R,
Rostas John A P,
Dunkley Peter R
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0750594.x
Subject(s) - autophosphorylation , calmodulin , calcium , phosphorylation , chemistry , zinc , protein kinase a , biochemistry , biophysics , microbiology and biotechnology , enzyme , biology , organic chemistry
Calcium/calmodulin‐dependent protein kinase II (CaMPK‐II) is a key regulatory enzyme in living cells. Modulation of its activity, therefore, could have a major impact on many cellular processes. We found that Zn 2+ has multiple functional effects on CaMPK‐II. Zn 2+ generated a Ca 2+ /CaM‐independent activity that correlated with the autophosphorylation of Thr 286 , inhibited Ca 2+ /CaM binding that correlated with the autophosphorylation of Thr 306 , and inhibited CaMPK‐II activity at high concentrations that correlated with the autophosphorylation of Ser 279 . The relative level of autophosphorylation of these three sites was dependent on the concentration of zinc used. The autophosphorylation of at least these three sites, together with Zn 2+ binding, generated an increased mobility form of CaMPK‐II on sodium dodecyl sulfate gels. Overall, autophosphorylation induced by Zn 2+ converts CaMPK‐II into a different form than the binding of Ca 2+ /CaM. In certain nerve terminals, where Zn 2+ has been shown to play a neuromodulatory role and is present in high concentrations, Zn 2+ may turn CaMPK‐II into a form that would be unable to respond to calcium signals.