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)

Rhinovirus (RV) is a major cause of wheezing in asthmatics and has been reported to cause beta2 adrenergic receptor hyporesponsiveness in human airway smooth muscle (HASM) via cellular secretion of interleukin (IL)-1beta. We studied the effects of IL-1beta and RV on cyclic adenosine monophosphate (cAMP) production in HASM cells. Chronic incubation with IL-1beta or RV caused a significant increase (approximately 3- and approximately 2-fold, respectively) in forskolin (FSK)-stimulated cAMP production, suggesting a sensitization of adenylyl cyclase (AC). The observed augmentation of FSK-stimulated cAMP formation by IL-1beta was completely abrogated by pretreatment with an IL-1 receptor antagonist or cycloheximide, demonstrating that the effect is mediated via the IL-1 receptor 1 (IL-1R1) and that de novo protein synthesis is required. In contrast, RV-induced AC sensitization was not mediated via the IL-1R1 but was observed to be protein kinase C-dependent. We suggest that the sensitization of AC observed after exposure to IL-1beta or RV infection is a cellular defense mechanism to promote pathways that induce relaxation in the inflamed airway.
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PMID:Interleukin-1beta and rhinovirus sensitize adenylyl cyclase in human airway smooth-muscle cells. 1135 Aug 35

Embryos deficient for an essential gene may show complex phenotypes that reflect pleiotropic functions and non-cell-autonomous requirements for the encoded protein. The generation of mosaic animals, where most cells are wild type, but a few cells are mutant, is a powerful tool permitting the detailed analysis of the cell autonomous function of a gene, in a particular cell type, at cellular and subcellular resolutions. Here we apply this method to the analysis of the Cerebral Cavernous Malformations 3 (CCM3) pathway in Drosophila.The conserved CCM3 protein functions together with its binding partner, Germinal Center Kinase III (Wheezy/GckIII in Drosophila, MST3, STK24, and STK25 in human) in the regulation of tube morphogenesis (Bergametti et al. Am J Hum Genet. 76:42-51, 2005; Fidalgo et al. J Cell Sci. 123:1274-1284, 2010; Guclu et al. Neurosurgery. 57:1008-1013, 2005; Lant et al. Nat Commun. 6:6449, 2015; Song et al. Dev Cell. 25:507-519, 2013; Ceccarelli et al. J Biol Chem. 286:25056-25064, 2011; Rehain-Bell et al. Curr Biol. 27:860-867, 2017; Xu et al. Structure. 21:1059-1066, 2013; Zhang et al. Front Biosci. 17:2295-2305, 2012; Zhang et al. Dev Cell. 27:215-226, 2013; Zheng et al. J Clin Invest. 120:2795-2804, 2010). The Drosophila proteins play a role in the regulation of tube shape in the tracheal (respiratory) system, analogous to the role of the human proteins in the vascular system. To understand the cellular basis for tube dilation defects caused by loss of pathway function, we describe techniques for the generation and analysis of positively marked homozygous mutant GckIII tracheal cells, coupled with an "open book" preparation that can be subjected to immunofluorescent analysis. Dozens of mutant tracheal cells are generated per mosaic animal, and neighboring heterozygous cells in the same animal serve as ideal internal controls.
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PMID:Dissection of the Role of CCM Genes in Tubulogenesis Using the Drosophila Tracheal System as a Model. 3252 53