Ganglioside modulation of XXXX -dependent protein kinase and cyclic @entity377 phosphodiesterase in vitro.

@entity268 @entity7746 @entity6579 @entity95 @entity377 @entity1919 @entity4163
Purified @entity1919 -dependent protein kinase (cAK) catalytic subunit phosphorylated 180-, 49-, 31-, 19-, and 14-kilodalton (kDa) proteins of @entity95 sciatic nerve membranes. The ability of cAK to phosphorylate these membrane substrate proteins was inhibited by @entity7746 GM1, GD1a, and GT1b with half-maximal inhibitory concentration (I50) = 7-25 microM. Neutral glycolipids and @entity6579 were much less effective. @entity1919 ( @entity268 ) kinase phosphorylation of histone IIA was inhibited by GM1, GD1a, and GT1b (I50 = 115 microM, 75 microM, and 75 microM, respectively). Inhibition by GM1 was competitive with respect to histone (Ki = 108 microM). Autophosphorylation of @entity268 kinase was inhibited by GM1 (I50 = 15 microM). GT1b, GD1a, and GM1 half-maximally stimulated calmodulin-dependent cyclic @entity377 phosphodiesterase at 0.1 microM, 0.2 microM, and 0.3 microM, respectively. Although GT1b stimulated phosphodiesterase by increasing Vmax and decreasing Km (similar to calmodulin), GD1a and GM1 produced only an increase in Vmax. These results suggest that @entity4163 can modulate the activity of @entity268 kinase by both direct inhibition of the enzyme and indirect reduction of @entity268 levels through activation of phosphodiesterase. Through these mechanisms, @entity7746 may alter @entity268 -dependent protein phosphorylation and cell function within the nervous system.
