Two interaction sites on mammalian adenylyl cyclase type I and II: modulation by calmodulin and G(betagamma)

The Biochemical Journal
Susanne DielChristiane Kleuss

Abstract

Mammalian ACs (adenylyl cyclases) are integrating effector molecules in signal transduction regulated by a plethora of molecules in either an additive, synergistic or antagonistic manner. Out of nine different isoforms, each AC subtype uses an individual set of regulators. In the present study, we have used chimaeric constructs, point mutations and peptide competition studies with ACs to show a common mechanism of multiple contact sites for the regulatory molecules G(betagamma) and calmodulin. Despite their chemical, structural and functional variety and different target motifs on AC, G(betagamma) and calmodulin share a two-site-interaction mechanism with G(alphas) and forskolin to modulate AC activity. Forskolin and G(alphas) are known to interact with both cytosolic domains of AC, from inside the catalytic cleft as well as at the periphery. An individual interaction site located at C(1) of the specifically regulated AC subtype had been ascribed for both G(betagamma) and calmodulin. In the present study we now show for these two regulators of AC that a second isoform- and regulator-specific contact site in C(2) is necessary to render enzyme activity susceptible to G(betagamma) or calmodulin modulation. In addition to the PFAHL...Continue Reading

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Citations

Mar 21, 2009·Cellular and Molecular Life Sciences : CMLS·André Lopez, Laurence Salomé
Feb 4, 2010·Journal of Experimental Zoology. Part A, Ecological Genetics and Physiology·Elena Fabbri, Antonio Capuzzo
Jul 25, 2015·Molecular Pharmacology·Cameron S BrandCarmen W Dessauer
May 21, 2011·Cellular Signalling·Aislyn D W BoranRavi Iyengar

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