Summary
Recently, we characterized a cDNA clone that encodes a human brain adenylyl cyclase (HBAC1). In the present study, we identified a second population of mRNA suspected to encode a new brain adenylyl cyclase (HBAC2). The amino acid sequence of HBAC2 displays significant homology with HBAC1 in the highly conserved adenylyl cyclase domain (250 aminio acids), found in the 3′ cytoplasmic domain of all mammalian adenylyl cyclases. However, outside this domain, the homology is extremely low, suggesting that the corresponding mRNA originates from a different gene. We report here the first chromosomal localization of the adenylyl cyclase genes determined by in situ hybridization of human metaphase chromosomal spreads using human brain cDNA probes specific for each mRNA. The probe corresponding to HBAC1 exhibited a strong specific signal on chromosome 8q24, with a major peak in the band q24.2. In contrast, the HBAC2 probe hybridized to chromosome 5p15, with a major peak in the band p15.3. The two cDNAs hybridized at the two loci without any cross reactivity. Thus, in human brain, a heterogeneous population of adenylyl cyclase mRNAs is expressed, and the corresponding genes might be under the control of independent regulatory mechanisms.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- C:
-
catalytic part of adenylyl cyclase
- BBAC:
-
bovine brain
- HBAC:
-
human brain
- ROAC:
-
rat olfactory
- RLAC:
-
rat liver
- RTAC:
-
rat testis adenylyl cyclase
- G:
-
guanine nucleotide GTP binding protein (s, stimulatory; i, inhibitory)
References
Anagnou NP, Economou-Pachnis A, O'Brien SJ, Modi WS, Nienhuis AW, Tsichlis PN (1987) The human homolog of the Moloney leukemia virus integration 2 locus (MLV12) maps to band p14 of chromosome 5. Cytogenet Cell Genet 46:571
Anand-Srivastava MB, Sairam MR, Cantin M (1990) Ring-deleted analogs of atrial natriuertic factor inhibit adenylate cyclase/ cAMP system. Possible coupling of clearance atrial natriuretic factor receptors to adenlylate cyclase/cAMP signal transduction system. J Biol Chem 265:8566–8572
Arden KC, Boutin JM, Djiane J, Kelly PA, Cavenee WK (1990) The receptors for prolactin and growth hormone are localized in the same region of human chromosome 5. Cytogenet Cell Genet 53:161–165
Baas F, Bikker H, Geurts van Kessel A, Melsert R, Pearson PL, Vijlder JJM de, Ommen GJB van (1985) The human thyroglobulin gene: a polymorphic marker localized distal to c-Myc on chromosome 8 band q24. Hum Genet 69:138–143
Bakalyar HA, Reed RR (1990) Identification of a specialized adenylyl cyclase that may mediate odorant detection. Science 250:1403–1406
Dalla-Favera R, Bregni M, Erikson J, Patterson D, Gallo RC, Croce CM (1982) Human c-myc one gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells. Proc Natl Acad Sci USA 79:7824–7827
Dayhoff MO, Barker WC, Hunt LT (1983) Establishing homologies in protein sequences. Methods Enzymol 91:524–527
Feinstein PG, Schrader KA, Bakalyar HA, Tang WJ, Krupinski J, Gilman AG, Reed RR (1991) Molecular cloning and characterization of a Ca2+/calmodulin insensitive adenylyl cyclase from rat brain. Proc Natl Acad Sci USA 88:10173–10177
Fowler CJ, O-Neill C, Garlind A, Cowburn RF (1990) Alzheimer's disease: is there a problem beyond recognition? Trends Pharmacol Sci 11:183–184
Gao B, Gilman AG (1991) Cloning and expression of a widely distributed (type IV) adenylyl cyclase. Proc Natl Acad Sci USA 88:10178–10182
Gilman AG (1987) G proteins transducer of receptor-generated signals. Annu Rev Biochem 56:615–649
Kanehisa M (1984) Use of statistical criteria for screening potential homologies in nucleic acid sequences. Nucleic Acids Res 12:203–213
Krupinski J, Coussen F, Bakalyar HA, Tang WJ, Feinstein PG, Orth K, Slaughter C, Reed RR, Gilmann AG (1989) Adenylyl cyclase amino acid sequence: Possible channel or transporter-like structure. Science 244:1558–1564
Kyte J, Doolittle RF (1982) A simple method for displaying the hydropathic character of a protein. J Mol Biol 157:105–132
Leitman DC, Andersen JW, Kuno T, Kamisaki Y, Hang JK, Murad F (1986) Identification of multiple binding sites for atrial natriuretic factor by affinity cross-linking in cultured endothelial cells. J Biol Chem 261:11650–11655
Lowe DG, Klisak I, Sparkes RS, Mohandas T, Goeddel DV (1990) Chromosomal distribution of three members of the human natriuretic receptor/guanylyl cyclase gene family. Genomics 8:304–312
Lyons J, Landis C, Harsh G, Vallar L, Grünewald K, Feichtinger H, Dun QY, Clark OL, Kawasaki E, Bourne HR, McCormick F (1990) Two G protein oncogenes in human endocrine tumors. Science 249:655–659
Mattei MG, Philip N, Passage E, Moisan JP, Mandel JL, Mattei JF (1985) DNA probe localization at 18p113 by in situ hybridization and idenfication of small supernumerary chromosome. Hum Genet 69:268–271
Parma J, Stengel D, Gannagé MJ, Poyard M, Barouki R, Hanoune J (1991) Sequence of a human brain adenylyl cyclase partial cDNA: Evidence for a consensus cyclase domain. Biochem Biophys Res Commun 179:455–462
Premont R, Iyengar R (1992) Liver adenylyl cyclases: structure and regulation by cAMP-dependent phosphorylation. Adenine nucleotides in cellular energy transfer and signal transduction. (In press)
Rogne S, Myklebost O, Stanley K, Geurts van Kessels A (1989) The gene for human complement C9 is on chromosome 5. Genomics 5:149–152
Tang WJ, Krupinski J, Gilman AG (1991) Expression and characterization of calmodulin-activated (type I) adenylyl cyclase. J Biol Chem 266:8595–8603
Taub R, Kirsch I, Morton C, Lenoir G, Swan D, Tronick S, Aaronson S, Leder P (1982) Translocation of c-myc gene into the immunoglobulin heavy chain locus in human Burkitt lymphoma and murine plasmacytoma cells. Proc Natl Acad Sci USA 79:7837–7841
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Stengel, D., Parma, J., Gannagé, M.H. et al. Different chromosomal localization of two adenylyl cyclase genes expressed in human brain. Hum Genet 90, 126–130 (1992). https://doi.org/10.1007/BF00210755
Issue Date:
DOI: https://doi.org/10.1007/BF00210755