Regulation of Ca2+/calmodulin-dependent protein kinase II by brain gangliosides

Koji Fukunaga, Eishichi Miyamoto, Thomas Soderling

Research output: Contribution to journalArticle

47 Citations (Scopus)

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
Volume54
Issue number1
StatePublished - 1990
Externally publishedYes

Fingerprint

Calcium-Calmodulin-Dependent Protein Kinase Type 2
Gangliosides
Brain
Calmodulin
Chemical activation
Peptides
Rats
Phosphotransferases
Proteolysis
G(M1) Ganglioside
Synaptic Membranes
Phosphorylation
Substrates
Threonine
Serine
Inhibitory Concentration 50
Calcium
Membranes

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Fukunaga, K., Miyamoto, E., & Soderling, T. (1990). Regulation of Ca2+/calmodulin-dependent protein kinase II by brain gangliosides. Journal of Neurochemistry, 54(1), 102-109.

Regulation of Ca2+/calmodulin-dependent protein kinase II by brain gangliosides. / Fukunaga, Koji; Miyamoto, Eishichi; Soderling, Thomas.

In: Journal of Neurochemistry, Vol. 54, No. 1, 1990, p. 102-109.

Research output: Contribution to journalArticle

Fukunaga, K, Miyamoto, E & Soderling, T 1990, 'Regulation of Ca2+/calmodulin-dependent protein kinase II by brain gangliosides', Journal of Neurochemistry, vol. 54, no. 1, pp. 102-109.
Fukunaga, Koji ; Miyamoto, Eishichi ; Soderling, Thomas. / Regulation of Ca2+/calmodulin-dependent protein kinase II by brain gangliosides. In: Journal of Neurochemistry. 1990 ; Vol. 54, No. 1. pp. 102-109.
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