Regulation of Ca2+/Calmodulin‐Dependent Protein Kinase II by Brain Gangliosides

Koji Fukunaga, Eishichi Miyamoto, Thomas R. Soderling

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52 Scopus citations


Abstract: Purified rat brain Ca2+/calmodulin‐dependent protein kinase II (CaM‐kinase II) is stimulated by brain gangliosides to a level of about 30% the activity obtained in the presence of Ca2+/calmodulin (CaM). Of the various gangliosides tested, GT1b was the most potent, giving half‐maximal activation at 25 μM. Gangliosides GD1a and GM1 also gave activation, but asialo‐GM1 was without effect. Activation was rapid and did not require calcium. The same gangliosides also stimulated the autophosphorylation of CaM‐kinase II on serine residues, but did not produce the Ca2+‐independent form of the kinase. Ganglioside stimulation of CaM‐kinase II was also present in rat brain synaptic membrane fractions. Higher concentrations (125‐250 μM) of GT1b, GD1a, and GM1 also inhibited CaM‐kinase II activity. This inhibition appears to be substrate‐directed, as the extent of inhibition is very dependent on the substrate used. The molecular mechanism of the stimulatory effect of gangliosides was further investigated using a synthetic peptide (CaMK 281‐309), which contains the CaM‐binding, inhibitory, and autophosphorylation domains of CaM‐kinase II. Using purified brain CaM‐kinase II in which these regulatory domains were removed by limited proteolysis, CaMK 281‐309 strongly inhibited kinase activity (IC50=0.2 μM). GT1b completely reversed this inhibition, but did not stimulate phosphorylation of the peptide on threonine‐286. These results demonstrate that GT1b can partially mimic the effects of Ca2+/CaM on native CaM‐kinase II and on peptide CaMK 281‐309.

Original languageEnglish (US)
Pages (from-to)102-109
Number of pages8
JournalJournal of neurochemistry
Issue number1
StatePublished - Jan 1990
Externally publishedYes


  • Calcium
  • Calmodulin
  • Gangliosides
  • Protein kinase
  • Protein phosphorylation

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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