PT  - JOURNAL ARTICLE
AU  - Lily I Jiang
AU  - Jennifer E Wang
AU  - Paul C. Sternweis
TI  - Regions on Adenylyl Cyclase VII Required for Selective Regulation by the G13 Pathway
AID  - 10.1124/mol.112.082446
DP  - 2012 Dec 10
TA  - Molecular Pharmacology
PG  - mol.112.082446
4099  - http://molpharm.aspetjournals.org/content/early/2012/12/10/mol.112.082446.short
4100  - http://molpharm.aspetjournals.org/content/early/2012/12/10/mol.112.082446.full
AB  - Regulation of multiple adenylyl cyclases (AC) provides unique inputs to mediate the synthesis of cAMP, a ubiquitous 2nd messenger that controls many aspects of cellular function. Upon stimulation by Gs, 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 G13 pathway. To better understand 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 Gβγ, activation of the G13 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 G13 pathway. A mutagenesis screen identified more specific regions of AC7 that differentially mediate its regulation by distinct pathways.