Abstract
Biochemical, immunological, and molecular cloning studies have suggested the existence of multiple forms of adenylyl cyclase (EC 4.6.1.1). An adenylyl cyclase cDNA clone (type II) was isolated from a rat brain library and found to encode a protein of 1090 amino acids that was homologous to but distinct from the previously described Ca2+/calmodulin-stimulated adenylyl cyclase from bovine brain. Expression of the type II cDNA in an insect cell line resulted in an increased level of adenylyl cyclase activity that was insensitive to Ca2+/calmodulin. Addition of activated Gs alpha protein to type II-containing membranes increased enzyme activity. The mRNA encoding the type II protein was expressed at high levels in brain tissue and at low levels in olfactory epithelium and lung. The existence of multiple adenylyl cyclase enzymes may provide for complex and distinct modes of biochemical regulation of cAMP levels in the brain.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bakalyar H. A., Reed R. R. Identification of a specialized adenylyl cyclase that may mediate odorant detection. Science. 1990 Dec 7;250(4986):1403–1406. doi: 10.1126/science.2255909. [DOI] [PubMed] [Google Scholar]
- Gao B. N., Gilman A. G. Cloning and expression of a widely distributed (type IV) adenylyl cyclase. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10178–10182. doi: 10.1073/pnas.88.22.10178. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jones D. T., Masters S. B., Bourne H. R., Reed R. R. Biochemical characterization of three stimulatory GTP-binding proteins. The large and small forms of Gs and the olfactory-specific G-protein, Golf. J Biol Chem. 1990 Feb 15;265(5):2671–2676. [PubMed] [Google Scholar]
- Jones D. T., Reed R. R. Molecular cloning of five GTP-binding protein cDNA species from rat olfactory neuroepithelium. J Biol Chem. 1987 Oct 15;262(29):14241–14249. [PubMed] [Google Scholar]
- Kozak M. Compilation and analysis of sequences upstream from the translational start site in eukaryotic mRNAs. Nucleic Acids Res. 1984 Jan 25;12(2):857–872. doi: 10.1093/nar/12.2.857. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Krupinski J., Coussen F., Bakalyar H. A., Tang W. J., Feinstein P. G., Orth K., Slaughter C., Reed R. R., Gilman A. G. Adenylyl cyclase amino acid sequence: possible channel- or transporter-like structure. Science. 1989 Jun 30;244(4912):1558–1564. doi: 10.1126/science.2472670. [DOI] [PubMed] [Google Scholar]
- Kyte J., Doolittle R. F. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. doi: 10.1016/0022-2836(82)90515-0. [DOI] [PubMed] [Google Scholar]
- Livingstone M. S., Sziber P. P., Quinn W. G. Loss of calcium/calmodulin responsiveness in adenylate cyclase of rutabaga, a Drosophila learning mutant. Cell. 1984 May;37(1):205–215. doi: 10.1016/0092-8674(84)90316-7. [DOI] [PubMed] [Google Scholar]
- Mollner S., Pfeuffer T. Two different adenylyl cyclases in brain distinguished by monoclonal antibodies. Eur J Biochem. 1988 Jan 15;171(1-2):265–271. doi: 10.1111/j.1432-1033.1988.tb13785.x. [DOI] [PubMed] [Google Scholar]
- Pace U., Hanski E., Salomon Y., Lancet D. Odorant-sensitive adenylate cyclase may mediate olfactory reception. Nature. 1985 Jul 18;316(6025):255–258. doi: 10.1038/316255a0. [DOI] [PubMed] [Google Scholar]
- Pfeuffer E., Mollner S., Lancet D., Pfeuffer T. Olfactory adenylyl cyclase. Identification and purification of a novel enzyme form. J Biol Chem. 1989 Nov 5;264(31):18803–18807. [PubMed] [Google Scholar]
- Rosenberg G. B., Storm D. R. Immunological distinction between calmodulin-sensitive and calmodulin-insensitive adenylate cyclases. J Biol Chem. 1987 Jun 5;262(16):7623–7628. [PubMed] [Google Scholar]
- Salomon Y. Adenylate cyclase assay. Adv Cyclic Nucleotide Res. 1979;10:35–55. [PubMed] [Google Scholar]
- Smigel M. D. Purification of the catalyst of adenylate cyclase. J Biol Chem. 1986 Feb 5;261(4):1976–1982. [PubMed] [Google Scholar]
- Tang W. J., Krupinski J., Gilman A. G. Expression and characterization of calmodulin-activated (type I) adenylylcyclase. J Biol Chem. 1991 May 5;266(13):8595–8603. [PubMed] [Google Scholar]
- Westcott K. R., La Porte D. C., Storm D. R. Resolution of adenylate cyclase sensitive and insensitive to Ca2+ and calcium-dependent regulatory protein (CDR) by CDR-sepharose affinity chromatography. Proc Natl Acad Sci U S A. 1979 Jan;76(1):204–208. doi: 10.1073/pnas.76.1.204. [DOI] [PMC free article] [PubMed] [Google Scholar]