Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

SPOC1 cells, which are a mucin-secreting model of rat airway goblet cells, possess a luminal P2Y2 purinoceptor through which UTP, ATP, and ATPgammaS stimulate secretion with EC50 values of approximately 3 microM. PMA elicits mucin secretion with high EC50 (75 nM) and saturation (300 nM) values. For the first time in airway mucin-secreting cells, the PKC isoforms expressed and activated by a secretagogue were determined using RT-PCR/restriction-enzyme mapping and Western blotting. Five isoforms were expressed: cPKCalpha, nPKCdelta and -eta, and aPKCzeta and -iota/lambda. PMA caused cPKCalpha and nPKCdelta to translocate to the membrane fraction of SPOC1 cells; only nPKCdelta so responded to ATPgammaS. Membrane-associated nPKCdelta and mucin secretion increased in parallel with ATPgammaS concentration and yielded EC50 values of 2-3 microM and maximum values of 100 microM. Effects of PMA to increase membrane-associated cPKCalpha and nPKCdelta saturated at 30 nM, whereas mucin secretion saturated at 300 nM, which suggests a significant PKC-independent effect of PMA on mucin secretion. A prime alternate phorbol ester-receptor candidate is the C1-domain protein MUNC13. RT-PCR revealed the expression of ubiquitous (ub)MUNC13-2 and its binding partner, DOC2-gamma. Hence, P2Y2 agonists activate nPKCdelta in SPOC1 cells. PMA activates cPKCalpha and nPKCdelta at high affinity and stimulates a lower affinity PKC-independent pathway that leads to mucin secretion.
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PMID:Mucin secretion and PKC isoforms in SPOC1 goblet cells: differential activation by purinergic agonist and PMA. 1258 4

The Caenorhabditis elegans neuromuscular junction (NMJ) is one of the best studied synapses in any organism. A variety of genetic screens have identified genes required both for the essential steps of neurotransmitter release from motorneurons as well as the signaling pathways that regulate rates of neurotransmitter release. A number of these regulatory genes encode proteins that converge to regulate neurotransmitter release. In other cases genes are known to regulate signaling at the NMJ but how they act remains unknown. Many of the proteins that regulate activity at the NMJ participate in a network of heterotrimeric G-protein signaling pathways controlling the release of synaptic vesicles and/or dense-core vesicles (DCVs). At least four heterotrimeric G-proteins (Galphaq, Galpha12, Galphao, and Galphas) act within the motorneurons to control the activity of the NMJ. The Galphaq, Galpha12, and Galphao pathways converge to control production and destruction of the lipid-bound second messenger diacylglycerol (DAG) at sites of neurotransmitter release. DAG acts via at least two effectors, MUNC13 and PKC, to control the release of both neurotransmitters and neuropeptides from motorneurons. The Galphas pathway converges with the other three heterotrimeric G-protein pathways downstream of DAG to regulate neuropeptide release. Released neurotransmitters and neuropeptides then act to control contraction of the body-wall muscles to control locomotion. The lipids and proteins involved in these networks are conserved between C. elegans and mammals. Thus, the C. elegans NMJ acts as a model synapse to understand how neuronal activity in the human brain is regulated.
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PMID:A network of G-protein signaling pathways control neuronal activity in C. elegans. 1961 33