text: Regions on adenylyl cyclase VII required for selective regulation by the G13 pathway.
  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 Gβγ, 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.
entities.id: T10 T11 T12 T13 T14 T15 T16 T17 T18 T19 T1 T20 T21 T22 T23 T24 T25 T26 T2 T3 T4 T5 T6 T7 T8 T9
entities.type: GENE-N GENE-N GENE-Y GENE-N GENE-Y GENE-Y GENE-Y GENE-Y GENE-N GENE-Y CHEMICAL GENE-Y GENE-N GENE-N GENE-Y GENE-Y GENE-Y GENE-Y CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-Y GENE-N GENE-N
entities.text: adenylyl cyclases AC AC7 AC G(13) AC7 AC2 AC7 Gβγ G(13) adenylyl AC7 C1b domain C1a domain AC7 G(13) adenylyl cyclase VII G13 cAMP cAMP N cAMP adenylyl AC7 G(s) ACs