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Description
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The membrane-bound adenylyl cyclases (ACs) represent one of the major families ofeffector enzymes for G protein-coupled receptors (GPCRs). Using the high inter-specieshomology of mammalian AC isoforms, nine Adenylyl cyclase (AC) isoforms, encoded byseparate genes, have been identified until today. Human adenylate cyclase genescomprise of 11 to 26 exons, which are distributed over 16 to 430kb. The expression profileof these 9 AC isoforms in a panel of 16 human tissues and in human embryonic kidney(HEK) cells have been demonstrated earlier (1). The cAMP synthesizing enzymes are foundin two forms: cytosolic (soluble) and membrane-bound (particulate). Stimulation ofadenylate cyclases produce cAMP form ATP in response to the activation of GPCRs byvarious hormones, neurotransmitters and other regulatory molecules. cAMP, insubsequent steps down the signal transduction pathway, can stimulate cAMP-dependentprotein kinase A (cPKA), and several other target molecules. Activation of cPKA canphosphorylate a broad range of substrates that regulate various metabolic pathways, geneexpression, and affect memory functions etc. , (3, 4). The stimulation of adenylate cyclasesstarts with interactions with GPCRs mediated signals initiated by Gs and Gi heterotrimericG-proteins. The interaction of GPCR agonist (eg. Interaction of isopreternol to beta2receptors) catalyses the exchange of GDP to GTP that is bound to G proteins. The GTPbinding reduces the affinity of Gs to other GTP binding proteins and Gs-GTP complexstimulate the adenylate cyclase (5). In last several years, new members of particulate andsoluble adenylate cyclase family have been identified and significant progress is made inunderstanding of the molecular mechanisms that underlie the regulation of these familiesof enzymes. The Ca2+/calmodulin-stimulated adenylyl cyclase (AC) isoforms AC1 and AC8,couple NMDA receptor activation to cAMP signaling pathways in neurons and are importantfor development, learning and memory, drug addiction and persistent pain. PAC8 has beenlinked to interleukin induced cell differentiation of vascular smooth muscle in to secretorycells (6).
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