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Publication : Regions on adenylyl cyclase VII required for selective regulation by the G13 pathway.

First Author  Jiang LI Year  2013
Journal  Mol Pharmacol Volume  83
Issue  3 Pages  587-93
PubMed ID  23229509 Mgi Jnum  J:261837
Mgi Id  MGI:6158806 Doi  10.1124/mol.112.082446
Citation  Jiang LI, et al. (2013) Regions on adenylyl cyclase VII required for selective regulation by the G13 pathway. Mol Pharmacol 83(3):587-93
abstractText  Regulation of multiple adenylyl cyclases (AC) provides unique inputs to mediate the synthesis of cAMP, a ubiquitous second messenger that controls many aspects of cellular function. On stimulation by G(s), the activities of ACs can be further selectively modulated by other pathways to ensure precise control of intracellular cAMP responses to specific stimuli. Recently, we reported that one of the AC isoforms, AC7, is uniquely regulated by the G(13) pathway. To understand more fully the molecular mechanism of this regulation, we compared the regulation of AC7 with that of AC2 in bone marrow-derived macrophages devoid of AC7. Although both enzymes could fully restore regulation of cAMP by Gbetagamma, activation of the G(13) pathway preferentially synergized with AC7. Exchange of domains between the two isoforms indicates that the C1b domain and the N-terminus of the C1a domain are important for directing selective regulation of AC7 by the G(13) pathway. A mutagenesis screen identified more specific regions of AC7 that differentially mediate its regulation by distinct pathways.
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