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14-3-3 Proteins directly regulate Ca(2+)/calmodulin-dependent protein kinase kinase alpha through phosphorylation-dependent multisite binding



14-3-3 Proteins directly regulate Ca(2+)/calmodulin-dependent protein kinase kinase alpha through phosphorylation-dependent multisite binding



Febs Letters 582(5): 661-665



Ca(2+)/calmodulin-dependent protein kinase kinase alpha (CaMKKalpha) plays critical roles in the modulation of neuronal cell survival as well as many other cellular activities. Here we show that 14-3-3 proteins directly regulate CaMKKalpha when the enzyme is phosphorylated by protein kinase A on either Ser74 or Ser475. Mutational analysis revealed that these two serines are both functional: the CaMKKalpha mutant with a mutation at either of these residues, but not the double mutant, was inhibited significantly by 14-3-3. The mode of regulation described herein differs the recently described mode of 14-3-3 regulation of CaMKKalpha.

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Accession: 051027436

Download citation: RISBibTeXText

PMID: 18242179

DOI: 10.1016/j.febslet.2008.01.037


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