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)

Phospholipase Cbeta3 (PLCbeta3) and PLCbeta4 are the two major isoforms in cerebellar Purkinje cells (PCs), displaying reciprocal expression across the cerebellum. Here, we examined subcellular distribution of PLCbeta3 in the mouse cerebellum by producing specific antibody. PLCbeta3 was detected as a particulate pattern of immunostaining in various PC elements. Like PLCbeta4, PLCbeta3 was richly distributed in somatodendritic compartments, where it was colocalized with molecules constituting the metabotropic glutamate receptor (mGluR1) signalling pathway, i.e. mGluR1alpha, G alpha q/G alpha 11 subunits of G q protein, inositol 1,4,5-trisphosphate receptor IP3R1, Homer1, protein kinase C PKCgamma, and diacylglycerol lipase DAGLalpha. Unlike PLCbeta4, PLCbeta3 was also distributed at low to moderate levels in PC axons, which were intense for IP3R1 and PKCgamma, low for G alpha q/G alpha 11, and negative for mGluR1alpha, Homer1, and DAGLalpha. By immunoelectron microscopy, PLCbeta3 was preferentially localized around the smooth endoplasmic reticulum in spines, dendrites, and axons of PCs, and also accumulated at the perisynapse of parallel fibre-PC synapses. Consistent with the ultrastructural localization, PLCbeta3 was biochemically enriched in the microsomal and postsynaptic density fractions. These results suggest that PLCbeta3 plays a major role in mediating mGluR1-dependent synaptic transmission, plasticity, and integration in PLCbeta3-dominant PCs, through eliciting Ca2+ release, protein phosphorylation, and endocannabinoid production at local somatodendritic compartments. Because PLCbeta3 can be activated by G betagamma subunits liberated from Gi/o and Gs proteins as well, axonal PLCbeta3 seems to modulate the conduction of action potentials through mediating local Ca2+ release and protein phosphorylation upon activation of a variety of G protein-coupled receptors other than mGluR1.
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PMID:Phospholipase Cbeta3 is distributed in both somatodendritic and axonal compartments and localized around perisynapse and smooth endoplasmic reticulum in mouse Purkinje cell subsets. 1729 1

Beta-arrestins-1 and 2 are known to play important roles in desensitization of membrane receptors and facilitation of signal transduction pathways. It has been previously shown that beta-arrestins are required for signal termination, internalization, and ERK1/2 activation downstream of protease-activated-receptor-2 (PAR-2), but it is unclear whether they are functionally redundant or mediate specific events. Here, we demonstrate that in mouse embryonic fibroblasts (MEFs) from beta-arrestin-1/2 knockout mice, G alpha q signaling by PAR-2, as measured by mobilization of intracellular Ca(2+), is prolonged. Only expression of beta-arrestin-1 shortened the signal duration, whereas either beta-arrestin-1 or 2 was able to restore PKC-induced receptor desensitization. Beta-arrestin-1 also mediated early, while beta-arrestin-2 mediated delayed, receptor internalization and membrane-associated ERK1/2 activation. While beta-arrestin-1 colocalized with a lysosomal marker (LAMP-1), beta-arrestin-2 did not, suggesting a specific role for beta-arrestin-1 in lysosomal receptor degradation. Together, these data suggest distinct temporal and functional roles for beta-arrestins in PAR-2 signaling, desensitization, and internalization.
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PMID:Differential effects of beta-arrestins on the internalization, desensitization and ERK1/2 activation downstream of protease activated receptor-2. 1744 37

The physiological effects of many extracellular neurotransmitters, hormones, growth factors, and other stimuli are mediated by receptor-promoted activation of phospholipase C (PLC) and consequential activation of inositol lipid signaling pathways. These signaling responses include the classically described conversion of phosphatidylinositol(4,5)P(2) to the Ca(2+)-mobilizing second messenger inositol(1,4,5)P(3) and the protein kinase C-activating second messenger diacylglycerol as well as alterations in membrane association or activity of many proteins that harbor phosphoinositide binding domains. The 13 mammalian PLCs elaborate a minimal catalytic core typified by PLC-d to confer multiple modes of regulation of lipase activity. PLC-b isozymes are activated by Gaq- and Gbg-subunits of heterotrimeric G proteins, and activation of PLC-g isozymes occurs through phosphorylation promoted by receptor and non-receptor tyrosine kinases. PLC-e and certain members of the PLC-b and PLC-g subclasses of isozymes are activated by direct binding of small G proteins of the Ras, Rho, and Rac subfamilies of GTPases. Recent high resolution three dimensional structures together with biochemical studies have illustrated that the X/Y linker region of the catalytic core mediates autoinhibition of most if not all PLC isozymes. Activation occurs as a consequence of removal of this autoinhibition.
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PMID:The phospholipase C isozymes and their regulation. 2240 74


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