The Kinase C Substrate Protein B-50 and Feedback Control of Synaptic Signal Transduction
Muscarinic receptor activation of rat hippocampus results in phosphodiesteratic cleavage of phosphatidylinositol 4,5-bisphos-phate (PIP2) yielding diacylglycerol (DG) and inositoltrisphospha-te (IP3). The latter is thought to mobilize calcium from intracellular stores, whereas DG activates protein kinase C. The predominant substrate protein for kinase C in the synaptic plasma membrane is protein B-50 (Mr 48 kDa, IEP 4.5). An increase in the degree of phosphorylation of B-50 is parallelled by an inhibition of phosphatidylinositol 4-phosphate (PIP) kinase, presumably rendering less PIP2 available for further receptor-mediated hydrolysis. Peptides derived from melanocortins are known to inhibit protein kinase C and therefore may counteract the negative feedback exerted by DG. As B-50 in the adult rat brain is predominantly localized in presynaptic terminals, this effect of melanocortins may underly a presynaptic modulation of neurotransmission. The potential physiological importance of such a modulation is adstructed by the role of protein kinase C in ACTH-induced grooming behavior in the rat and by the modulation by ACTH of muscarinic-activated hydrolysis of PIP2 in rat hippocampal slices.
KeywordsProtein Kinase Synaptic Plasma Membrane Excessive Grooming Muscarinic Receptor Activation Phorbol Diester
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