Substrate phosphorylation in the protein kinase Cgamma knockout mouse.
The phosphorylation state of three identified neural-specific protein kinase C substrates (RC3, GAP-43/B-50, and MARCKS) was monitored in hippocampal slices of mice lacking the gamma-subtype of protein kinase C and wild-type controls by quantitative immunoprecipitation following 32Pi labeling. Depolarization with potassium, activation of glutamate receptors with glutamate, or direct stimulation of protein kinase C with a phorbol ester increased RC3 phosphorylation in wild-type animals but failed to affect RC3 phosphorylation in mice lacking the gamma-subtype of protein kinase C. Our results suggests the following biochemical pathway: activation of a postsynaptic (metabotropic) glutamate receptor stimulates the gamma-subtype of protein kinase C, which in turn phosphorylates RC3. The inability to increase RC3 phosphorylation in mice lacking the gamma-subtype of protein kinase C by membrane depolarization or glutamate receptor activation may contribute to the spatial learning deficits and impaired hippocampal LTP observed in these mice.
Ramakers
G M
GM
Rudolf Magnus Institute for Neurosciences, Department of Medical Pharmacology, Unversiteitsweg 100, 3584 CG Utrecht, The Netherlands. geert.ramakers@basalmed.uio.no
Gerendasy
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DD
de Graan
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PN
D000818:Animals; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D019922:GAP-43 Protein / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000235:genetics*; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051579:Neurogranin; D010766:Phosphorylation; D011493:Protein Kinase C / Q000235:genetics*; D011506:Proteins / Q000378:metabolism; D013379:Substrate Specificity
D002148:Calmodulin-Binding Proteins; D019922:GAP-43 Protein; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; C000619711:Marcks protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C496650:Nrgn protein, mouse; D011506:Proteins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D051579:Neurogranin; C087857:protein kinase C gamma; D011493:Protein Kinase C