A novel peptide which stimulates adenylate cyclase: Molecular cloning and characterization of the ovine and human cDNAs

Kimura, Chiharu; Ohkubo, Shoichi; Ogi, Kazuhiro; Hashimoto, Masaki; Itoh, Yoshio; Onda, Haruo; Miyata, Atsuro; Jiang, Libin; Dahl, Raymond R.; Stibbs, Henry H.; Arimura, Akira; Fujino, Masahiko

doi:10.1016/0006-291x(90)91914-e

Cited by 297 publications

(87 citation statements)

References 9 publications

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“…The signal peptide of the salmon GHRHPACAP precursor has a hydrophobic core and has two amino acids less than the signal peptide of the ovine [8], human [l, 81 and rat [9] PACAP precursors ( Fig. S2).…”

Section: Organization Of the Ghrwpacap Precursormentioning

confidence: 99%

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Two salmon neuropeptides encoded by one brain cDNA are structurally related to members of the glucagon superfamily

Parker

Coe

Dixon

et al. 1993

European Journal of Biochemistry

111

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A cDNA that codes for two peptides in the glucagon superfamily has been isolated from sockeye salmon brain. The first peptide is related to growth hormone-releasing hormone (GHRH), which has high sequence similarity with PACAP-related peptide. The second peptide is structurally related to vasoactive intestinal peptide, which is also related to a newly identified peptide in mannals, pituitary adenylate-cyclase-activating polypeptide (PACAP). The salmon precursor contains 173 amino acids and has dibasic and monobasic enzyme-processing sites for cleavage of a 45-aminoacid GHRH-like peptide with a free C-terminus and a 38-amino-acid PACAP with an amidated C-terminus. The salmon GHRH-like peptide has 40% amino acid sequence identity with the human GHRH and 56% identity with human PACAP-related peptide. The 38-amino-acid salmon PACAP is highly conserved (89-92% identity) with only three or four amino acid substitutions compared with the human, ovine and rat 38-amino-acid PACAP.Not previously reported for mammalian species, a short precursor coding for only one peptide exists in salmon in addition to the long precursor coding for two peptides. In the short precursor, the coding region for GHRH is deleted leaving the PACAP-coding region in a correct reading frame. This provides one possible control mechanism for an increased expression of one peptide (PACAP) without the concomitant increase in the other peptide (GHRH) as occurs in a double-peptide precursor. The importance of the 3' non-translated region of the salmon GHRWPACAP precursor in the regulation of translation is suggested by its 70% nucleotide sequence identity to the 3' non-translated regions of the mammalian PACAP precursors. The structural organization of the salmon GHRW PACAP precursor provides a possible evolutionary scheme for precursors that contain tandem peptides in the glucagon superfamily.The glucagon superfamily includes glucagon, vasoactive intestinal polypeptide (VIP), peptide histidine methionine (PHM), peptide histidine isoleucine (PHI), secretin, gastric inhibitory peptide, growth hormone-releasing hormone (GHRH), helospectin and helodermin. Recently, two new candidates, pituitary adenylate-cyclase-activating polypeptide (PACAP) and PACAP-related peptide (PRP) were identified in mammals. Structurally, they resemble VIP and GHRH, respectively. PACAP has been classified as a member of the glucagon superfamily not only because of the close sequence similarity with VIP and GHRH [l], but also because of the similarity of the PACAP-gene structure [2] to that of the VIP gene Abbreviations. ACTH, adrenocorticotropic hormone ; FSH. follicle stimulating hormone; GH, growth hormone; GHRH, growthhormone-releasing hormone ; human, h; LIB, library; PACAP, pituitary adenylate-cyclase-activating polypeptide; PCR, polymerase chain reaction ; PHI, peptide histidine isoleucine; PHM, peptide histidine methionine; PRP, PACAP-related peptide; RACE rapid amplification of cDNA ends; VIP, vasoactive intestinal peptide.Note. The novel nucleotide sequence data publish...

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Section: Organization Of the Ghrwpacap Precursormentioning

confidence: 99%

“…The cDNA has been cloned from ovine hypothalamus [8], human testis [l, 81 and rat brain [9]. The human gene has also been studied [2].…”

mentioning

confidence: 99%

Two salmon neuropeptides encoded by one brain cDNA are structurally related to members of the glucagon superfamily

Parker

Coe

Dixon

et al. 1993

European Journal of Biochemistry

111

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“…PACAPand PACAPcoexist in mammalian tissues [ 1,3] and derive from the same precursor [l-3]. Their processing remains to be established and, by analogy with the glucagon system [ 181, both PACAPs may conceivably result from independent, tissuespecific, cleavage rather than from successive cleavage involving PACAPas a PACAPprecursor.…”

Section: Adenylate Cyclase Assaymentioning

confidence: 99%

The two forms of the pituitary adenylate cyclase activating polypeptide (PACAP (1–27) and PACAP (1–38)) interact with distinct receptors on rat pancreatic AR 4‐2J cell membranes

et al. 1991

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The existence of specific receptors for the two PACAPs (Pituirary Adenylate Cyclase Activating Peptides of 27 and 38 amino acids) was previously demonstrated on membranes from the pancreatic acinar cell line AR 4‐2J (Buscail et al., FEBS Lett. 202, 77–81, 1990) by [125I]PACAP‐27 binding. Here we demonstrate, by comparing Scatchard analysis of saturation curves and competition binding curves obtained with [125I]PACAP‐27 and [125I]PACAP‐38 as radioligands, the coexistence of two classes of receptors : 1/ PACAP‐A receptors that recognize PACAP‐27 and PACAP‐38 with the same high affinity (K d 0.3 nM) and 2/ PACAP‐B receptors that recognize PACAP‐38 with a high affinity (K d 0.3 nM) and PACAP‐27 with a lower affinity (K d 30 nM). These two receptors are coupled to adenylate cyclase but can be clearly distinguished by the ability of PACAP(6–27) to specifically inhibit PACAP‐27 adenylate cyclase activation.

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“…cDNA cloning of the PACAP precursor from ovine, rat and human sources revealed that the primary structures of human [3] and rat [4] PACAP molecules are identical to the ovine peptide, suggesting a highly conserved and crucial role as a neuropeptide and/or as a gastrointestinal hormone. In superfused rat pituitary cells, PACAP stimulates the release of adrenocorticotropin, growth hormone, prolactin and luteinizing hormone [2].…”

Section: Pituitarymentioning

confidence: 99%

Characterization of a guanosine‐nucleotide‐binding‐protein‐coupled receptor for pituitary adenylate‐cyclase‐activating polypeptide on plasma membranes from rat brain

Schäfer

Schwarzhoff

Creutzfeldt

et al. 1991

European Journal of Biochemistry

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Pituitary adenylate-cyclase-activating polypeptide (PACAP), a novel brain-gut hormone, was isolated from ovine hypothalami and represents the latest mammalian member of the secretinglucagon peptide family. PACAP exists in two C-terminally amidated molecular forms, PACAP(1-27) and PACAP(1-38), comprising 27 or 38 amino acid residues, respectively. In order to identify a specific receptor for PACAP, we studied binding of '251-labelled PACAP(1-27) to plasma membranes from rat brain. We identified a single high-affinity binding site (Kd, 340 pM and B,,,, 3.34 pmol/mg), specific for synthetic PACAP(1-38) and PACAP(1-27). Hormone binding was reversible and time, protein and temperature dependent. In contrast, neither the analogues PACAP(1 -23), and PACAP(3 -25), nor vasoactive intestinal peptide (VIP), secretin and growth-hormone-releasing factor (GRF) revealed significant binding at concentrations up to 1 FM. A specific receptor protein, with an apparent molecular mass of 60 kDa, was identified by means of affinity cross-linking with disuccinimidyl suberate (DSS) and ethylene glycol disuccinimidyl suberate (EGS). PACAP receptors are associated with a GTP-binding protein as determined by the influence of different nucleotides on PACAP binding. PACAP-binding activity was solubilized with the detergents 3-[(3-cholamidopropyl)dimethylammonio]2-hydroxy-l -propane sulfonate (Chapso) or Triton X-100 and was characterized as a high-molecular-mass receptor complex (400 kDa) by nonreducing size-exclusion chromatography on Sepharose CL-6B. These data imply the following: high-affinity PACAP receptors are expressed abundantly on rat-brain plasma membranes; PACAP receptors are specific for PACAP and show no affinity for VIP, secretin and GRF; the PACAP receptor molecule has an apparent molecular mass of 60 kDa; the PACAP receptor complex is associated with a GTP-binding protein. Pituitaryadenylate-cyclase-activating polypeptide (PACAP) has been recently isolated from ovine hypothalamic extracts [l]. This C-terminally amidated peptide comprises 38 or 27 amino acid residues and reveals a high potency for adenylate-cyclase activation on rat pituitary cells [2]. PACAP(1-27) possesses full biological activity and shows 68% similarity to vasoactive intestinal peptide (VIP). Therefore, PACAP is regarded as a novel member of the secretin- Dedication. This publication is dedicated to Prof. Dr Norbert Hilschmann, Max-Planck-Institute for Experimental Medicine, Gottingen on the occasion of his 60th birthday. glucagon family, a group of structurally related regulatory peptides.cDNA cloning of the PACAP precursor from ovine, rat and human sources revealed that the primary structures of human [3] and rat [4] PACAP molecules are identical to the ovine peptide, suggesting a highly conserved and crucial role as a neuropeptide and/or as a gastrointestinal hormone. In superfused rat pituitary cells, PACAP stimulates the release of adrenocorticotropin, growth hormone, prolactin and luteinizing hormone [2]. However, the regional distribution of PACA...

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A novel peptide which stimulates adenylate cyclase: Molecular cloning and characterization of the ovine and human cDNAs

Cited by 297 publications

References 9 publications

Two salmon neuropeptides encoded by one brain cDNA are structurally related to members of the glucagon superfamily

Two salmon neuropeptides encoded by one brain cDNA are structurally related to members of the glucagon superfamily

The two forms of the pituitary adenylate cyclase activating polypeptide (PACAP (1–27) and PACAP (1–38)) interact with distinct receptors on rat pancreatic AR 4‐2J cell membranes

Characterization of a guanosine‐nucleotide‐binding‐protein‐coupled receptor for pituitary adenylate‐cyclase‐activating polypeptide on plasma membranes from rat brain

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