This review explores the origins, diversity and functions of guanylyl cyclases in cellular organisms. In eukaryotes both cGMP and cAMP are produced by the conserved class III cyclase domains, while prokaryotes use five more unrelated catalysts for cyclic nucleotide synthesis. The class III domain is found embedded in proteins with a large variety of membrane topologies and other functional doma...

cAMP signaling pathways can both stimulate and inhibit the development of cancer; however, the sources of cAMP important for tumorigenesis remain poorly understood. Soluble adenylyl cyclase (sAC) is a non-canonical, evolutionarily conserved, nutrient- and pH-sensing source of cAMP. sAC has been implicated in the metastatic potential of certain cancers, and it is differentially localized in huma...

The alpha 2A-adrenergic receptor (adrenoceptor) was stably expressed in AtT20 mouse pituitary tumor cells; adrenoceptor agonists inhibited adenylyl cyclase, inhibited voltage-dependent calcium currents, and increased inwardly rectifying potassium currents. An aspartic acid residue (Asp79) highly conserved among guanine nucleotide-binding protein (G protein)-coupled receptors was mutated to aspa...

Background: Progesterone induces the resumption of meiosis (maturation) Addresses: *Loeb Research Institute, Ottawa Hospital, Ottawa K1Y 4E9, Canada. in Xenopus oocytes through a nongenomic mechanism involving inhibition † Department of Biochemistry, Microbiology, and of an oocyte adenylyl cyclase and reduction of intracellular cAMP. However, Immunology, ‡ Department of Medicine, progesterone a...

The cAMP and ERK/MAP kinase (MAPK) signal transduction pathways are critical for hippocampus-dependent memory, a process that depends on CREB-mediated transcription. However, the extent of crosstalk between these pathways and the downstream CREB kinase activated during memory formation has not been elucidated. Here we report that PKA, MAPK, and MSK1, a CREB kinase, are coactivated in a subset o...

The characteristics of inhibitory regulation of adenylyl cyclase V/VI by Ca and G proteins were examined in dispersed gastric smooth muscle cells. The mechanisms were evoked separately, sequentially, or concurrently using ligand-gated and G protein-coupled receptor agonists and receptor-independent probes (e.g, thapsigargin). During the initial phase of agonist stimulation, a,b-methylene-ATP, U...

Incubation of human thrombocytes in the presence of [3H]palmitic acid leads to incorporation of this fatty acid into the alpha subunit of Gs as described [Linder et al., Proc. Natl. Acad. Sci. USA 90 (1993) 3675-3679; Degtyarev et al., Biochemistry 32 (1993) 8057-8061] but also into the catalyst of adenylyl cyclase which has not been recognized before. Treatment of labeled membranes with hydrox...

Spermatozoa undergo a poorly understood activation process induced by bicarbonate and mediated by cyclic adenosine 3',5'-monophosphate (cAMP). It has been assumed that bicarbonate mediates its effects through changes in intracellular pH or membrane potential; however, we demonstrate here that bicarbonate directly stimulates mammalian soluble adenylyl cyclase (sAC) activity in vivo and in vitro ...

The enzymic properties of adenylyl cyclase in purified membrane vesicles from human and boar spermatozoa are described. Plasma membrane vesicles, which appear to be right-side-out, show a marked increase in activity in the presence of the detergent Triton X-100, manganous ion and alkaline pH. Electron-microscope cytochemical assays indicated the presence of adenylyl cyclase in boar and human sp...

We have implemented a yeast genetic selection developed previously by our laboratory to identify mutant mammalian type V adenylyl cyclases insensitive to inhibition by G(ialpha.) One mutation isolated was localized to the first cytoplasmic domain at a Phe residue (position 400), which is conserved in all nine isoforms of membrane-bound mammalian adenylyl cyclase. Biochemical characterization of...