Adenylyl Cyclase Amino Acid Sequence: Possible Channel- or Transporter-Like Structure

Krupinski, John; Coussen, Françoise; Bakalyar, Heather A.; Tang, Wei; Feinstein, Paul; Orth, Kim; Slaughter, Clive A.; Reed, Randall R.; Gilman, Alfred G.

doi:10.1126/science.2472670

Cited by 722 publications

(315 citation statements)

References 51 publications

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“…Figure 2 shows the alignment of C-terminal regions of these ORFs and of the putative catalytic domains of adenylate cyclases. The regions near the C termini of these proteins containing about 180 amino acids showed 27.5 to 55.4% identity to each other, 29.7 to 35.2% identity to the adenylate cyclase of A. cylindrica (26), 25.9 to 31.4% identity to S. platensis CyaA (52), 29.4 to 35.0% identity to R. meliloti Cya1 (4), and 19.2 to 20.9% identity to the C1a region of bovine type I adenylate cyclase (28). We concluded that these ORFs in p665SK, pQ3SK, pQ2-1SK, p667SK, and pQ6-2SK are the adenylate cyclase genes of Anabaena strain PCC 7120 and designated them cyaA, cyaB1, cyaB2, cyaC, and cyaD, respectively.…”

Section: Resultsmentioning

confidence: 99%

Isolation and characterization of multiple adenylate cyclase genes from the cyanobacterium Anabaena sp. strain PCC 7120

Katayama

Ohmori

1997

J Bacteriol

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Adenylate cyclase genes, designated cyaA, cyaB1, cyaB2, cyaC, and cyaD, were isolated from the filamentous cyanobacterium Anabaena sp. strain PCC 7120 by complementation of a strain of Escherichia coli defective for the presence of cya. These genes encoded polypeptides consisting of 735, 859, 860, 1,155, and 546 amino acid residues, respectively. Deduced amino acid sequences of the regions near the C-terminal ends of these cya genes were similar to those of catalytic domains of eukaryotic adenylate cyclases. The remaining part of each cya gene towards its N-terminal end showed a characteristic structure. CyaA had two putative membrane-spanning regions. Both CyaB1 and CyaB2 had regions that were very similar to the cyclic GMP (cGMP)-binding domain of cGMP-stimulated cGMP phosphodiesterase. CyaC consisted of four distinct domains forming sequentially from the N terminus: a response regulator-like domain, a histidine kinase-like domain, a response regulatorlike domain, and the catalytic domain of adenylate cyclase. CyaD contained the forkhead-associated domain in its N-terminal region. Expression of these genes was examined by reverse transcription-PCR. The transcript of cyaC was shown to be predominant in this cyanobacterium. The cellular cyclic AMP level in the disruptant of the cyaC mutant was much lower than that in the wild type.Cyclic AMP (cAMP) regulates various biological activities in both prokaryotes and eukaryotes. In prokaryotes, cAMP and cAMP receptor protein regulate gene expression (7). In eukaryotes, cAMP regulates enzyme activity (11), channel activity (42), and gene expression (34) via the cAMP-dependent protein kinase. In cyanobacteria, it has been reported that cellular cAMP content is affected by growth conditions (17,22), that cAMP concentration changes rapidly in response to light-off and light-on signals (37) or to a pH shift (36), and that cAMP interferes with the pattern formation of heterocysts (43). However, it is still unknown whether cAMP functions as an intracellular signal molecule in cyanobacteria.Recently, we isolated adenylate cyclase (cya) genes from the filamentous cyanobacteria Anabaena cylindrica (26) and Spirulina platensis (52). Regions near the C-terminal ends of the adenylate cyclases of both cyanobacteria showed significant structural similarity to the catalytic domain of the adenylate cyclase of eukaryotes but showed no homology to that of prokaryotes such as Escherichia coli. Furthermore, cyanobacterial adenylate cyclases appeared to be membrane oriented.To study the physiological functions of these adenylate cyclases, disruption or overexpression of cya genes is indispensable. Unfortunately, both A. cylindrica and S. platensis are not transformable, so they are not suitable for this purpose. In this study, we isolated cya genes from a transformable cyanobacterium, Anabaena sp. strain PCC 7120, and constructed mutants defective in cya genes. Some physiological properties of these mutants were determined. MATERIALS AND METHODSStrains and growth conditions. Anabaena sp. s...

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Section: Resultsmentioning

confidence: 99%

Isolation and characterization of multiple adenylate cyclase genes from the cyanobacterium Anabaena sp. strain PCC 7120

Katayama

Ohmori

1997

J Bacteriol

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“…4.6.1.1) is the enzyme that converts ATP to cAMP. To date, nine distinct isoforms of mammalian AC (designated I to IX) and two splice variants of the type VIII enzyme have been cloned and characterized (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Because of the diversity in their regulation, the various AC isoforms may be broadly divided into five groups.…”

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confidence: 99%

Characterization of soluble forms of nonchimeric type V adenylyl cyclases

Scholich

Barbier

Mullenix

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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Type V adenylyl cyclase (ACV) belongs to the family of Ca 2+ - inhibited cyclases. We have generated two soluble forms of the enzyme containing the C1 or C1a region (which lacks the C-terminal 112 amino acids) linked to the C2 domain and compared their regulation with the full-length ACV. All three forms of ACV were stimulated by the α subunit of the stimulatory G protein G s (G sα ) and forskolin. However, the synergistic stimulation by both these activators was markedly enhanced in the soluble enzymes. Moreover, the α subunit of the inhibitory G protein G i (G iα ) inhibited all forms of the enzyme, indicating that the regions for G sα and G iα interaction are preserved in the soluble forms. Ca 2+ inhibited forskolin-stimulated adenylyl cyclase (AC) activity of the full-length and C1-C2 forms of ACV but did not alter the activity of the C1a-C2 form. Maximal stimulation of AC activity by combination of G sα and forskolin obliterated the Ca 2+ -mediated inhibition of the full-length and C1-C2 forms of ACV. In 45 Ca 2+ overlay experiments, the C1-C2 but not the C1a-C2 soluble ACV bound Ca 2+ . Moreover, proteins corresponding to the C1a and C2 domains did not bind calcium. On the other hand, the proteins corresponding to C1 and its C-terminal 112 amino acids (C1b) bound 45 Ca 2+ . To our knowledge, this is the first report of nonchimeric soluble forms of AC in which regulation by G sα and G iα is preserved. Moreover, we demonstrate that the 112 amino acid C1b region of ACV is responsible for the binding of Ca 2+ and inhibition of enzyme activity.

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“…In contrast to receptors and G proteins, the effectors they regulate appear to have little in common. They include enzymes like adenylate cyclase (Krupinski et al, 1989), polyphosphoinositidespecific phospholipase C (Harden, 1989), cyclic GMP phosphodiesterase (Stryer, 1988) and phospholipase A2 (Burch et al, 1986), transporters for Mg2+ (Erdos et al, 1981) and possibly glucose (Kuroda et al, 1987), and ion channels that gate K+ (Yatani et al, 1987a), Ca2+ (Yatani et al, 1987b) or Na+ (Cantiello et al, 1989;Krapivinsky et al, 1989). The molecular details of the interactions between G proteins and effectors are so poorly understood that conserved features of their interactions may not yet have been revealed, but the present evidence suggests that this step in the sequence is probably the least conserved between signalling pathways (see below).…”

Section: Structure and Function In G Protein Signalling Pathwaysmentioning

confidence: 99%

The role of G proteins in transmembrane signalling

Taylor

1990

Biochemical Journal

226

113

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INTRODUCTIONIn some transmembrane signalling systems detection of the extracellular stimulus and generation of an intracellular response are properties of the same protein or protein complex. Binding of acetylcholine to the a subunits of the pentameric nicotinic receptor, for example, opens a cation-selective channel formed by parts of each of the receptor subunits, and insulin when it binds to the extracellular domain of its receptor activates a protein tyrosine kinase activity in the intracellular domain of the same protein. Rodbell and his collaborators (Rodbell et al., 1971) were the first to provide evidence for a more complex class of signalling pathway where the sensor and intracellular effector are separate proteins that communicate through a guanine nucleotide-dependent regulatory protein or G protein. The G protein cycles between inactive GDP-bound and active GTPbound forms. Activation is catalysed by receptors and deactivation is an intrinsic property of the G protein, its GTPase activity. The developments that followed Rodbell's pioneering studies have established that many different receptors regulate many intracellular effectors through a family of closely related G proteins (Citri & Schramm, 1980;Rodbell, 1980;Schramm & Selinger, 1984;Northup, 1985;Levitzki, 1988). Many excellent recent reviews have focused on various aspects of these interactions between receptors, G proteins and intracellular effectors (Casperson & Bourne, 1987;Gilman, 1987;Allende, 1988;Lochrie & Simon, 1988;Weiss et al., 1988;Chabre & Deterre, 1989;Ross, 1989;Houslay, 1990).The G protein cycle, at the centre of the conversation between receptors and their effectors, provides one solution to the compromise that cells must make between responding rapidly and being able to respond to very low concentrations of extracellular stimulus. In this review I will consider how different signalling mechanisms are adapted to the cellular processes they control by comparing the properties of the signalling pathways that involve G proteins with the simpler pathways that do not.

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Adenylyl Cyclase Amino Acid Sequence: Possible Channel- or Transporter-Like Structure

Cited by 722 publications

References 51 publications

Isolation and characterization of multiple adenylate cyclase genes from the cyanobacterium Anabaena sp. strain PCC 7120

Isolation and characterization of multiple adenylate cyclase genes from the cyanobacterium Anabaena sp. strain PCC 7120

Characterization of soluble forms of nonchimeric type V adenylyl cyclases

The role of G proteins in transmembrane signalling

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