N‐Terminal Splice Variants of the Type I PACAP Receptor: Isolation, Characterization and Ligand Binding/Selectivity Determinants

@article{Dautzenberg1999NTerminalSV,
  title={N‐Terminal Splice Variants of the Type I PACAP Receptor: Isolation, Characterization and Ligand Binding/Selectivity Determinants},
  author={Dautzenberg and Mevenkamp and Wille and Hauger},
  journal={Journal of Neuroendocrinology},
  year={1999},
  volume={11}
}
Three full‐length cDNAs encoding functional splice variants of the pituitary adenylate cyclase‐activating polypeptide (PACAP) type 1 receptor (PAC1) were isolated from Y‐79 retinoblastoma cells and human cerebellum. Although the third intracellular loops of the three splice variants were identical, their N‐terminal extracellular domains differed. The first full‐length PAC1 variant, PAC1normal (PAC1n), encoded the entire N‐terminus, whereas the second variant named PAC1short (PAC1s) was deleted… 
Characterization of novel splice variants of the PAC1 receptor in human neuroblastoma cells: Consequences for signaling by VIP and PACAP
TLDR
There may be a phenotypic switch in the expression of different PAC1 receptor amino terminal splice variants between embryonic and mature nervous system, indicating that regulation of this event may have an important role in VIP/PACAP function, particularly in the developing nervous system.
The functional recombinant first extracellular (EC1) domain of PACAP receptor PAC1 normal form (PAC1-EC1(N)) recognizes selective ligands and stimulates the proliferation of PAC1-CHO cells
TLDR
The results of MTT assays showed that PAC1-EC1(N) stimulated the viability of PAC-CHO cells but blocked the effects of maxadilan on the proliferation of CHO cells expressing PAC1 (PAC1-CHO), indicating that the functional soluble PAC1 -EC1 (N) may act as a regulator for the activation of PAC1.
Novel Splice Variants of Type I Pituitary Adenylate Cyclase-Activating Polypeptide Receptor in Frog Exhibit Altered Adenylate Cyclase Stimulation and Differential Relative Abundance.
TLDR
Two splice variants of the frog receptor that display additional amino acid cassettes in the third intracellular loop were characterized and a third splice variant of PAC1-R, exhibiting a completely different intrACEllular C-terminal domain, named PAC 1-Rmc has also been identified.
Identification of two novel chicken GHRH receptor splice variants: implications for the roles of aspartate 56 in the receptor activation and direct ligand receptor interaction.
TLDR
The findings not only suggest that cGHRHR variants may play a role in controlling normal pituitary functions, but also support that Asp(56) is nonessential for receptor activation and direct ligand-receptor interaction.
Characterization of the PAC1 Variants Expressed in the Mouse Heart
TLDR
Characterization of the molecular forms of PAC1 in mouse heart revealed the presence of four types of variant receptors harboring the N or S variant in the first extracellular domain (EC1 domain) with or without the HOP1 insert in the third intracellular cytoplasmic loop (IC3 loop).
Differential Intracellular Signaling through PAC1 Isoforms as a Result of Alternative Splicing in the First Extracellular Domain and the Third Intracellular Loop
TLDR
It is indicated that the combination of alternative splicing events in the EC1 domain and the IC3 loop create a variety of PAC1 isoforms, which in turn may contribute to the functional pleiotropism of PACAP.
Alternative Splicing of the Pituitary Adenylate Cyclase-activating Polypetide (PACAP) Receptor Contributes to Function of PACAP-27
Pituitary adenylate cyclase-activating polypeptide (PACAP)-27 and PACAP-38 are neuropeptides performing a variety of physiological functions. The PACAP-specific receptor PAC1 has several variants
Characterization of four receptor cDNAs: PAC1, VPAC1, a novel PAC1 and a partial GHRH in zebrafish
TLDR
PACAP and GHRH have widespread, overlapping target sites suggesting a coordinated role for these hormones in evolution, and their receptors were characterized in zebrafish.
Characterisation of the Mouse Vasoactive Intestinal Peptide Receptor Type 2 Gene, Vipr2, and Identification of a Polymorphic LINE-1-like Sequence That Confers Altered Promoter Activity
TLDR
The results suggest that the mouse Vipr2 gene may be differentially active in different mouse strains, depending on the presence of this LINE‐1‐like sequence in the promoter region.
Identification of PAC1 receptor isoform mRNAs by real-time PCR in rat suprachiasmatic nucleus.
TLDR
The results indicate that the phase-dependency of the actions of PACAP on SCN firing and circadian behaviour are not mediated by changes in the level of expression ofPAC1 receptor mRNA, nor by phase-dependent expression of PAC1 receptor variants with altered ligand binding, G-protein coupling or signalling characteristics.
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References

SHOWING 1-10 OF 87 REFERENCES
Isolation and Pharmacological Characterization of Two Functional Splice Variants of Corticotropin‐Releasing Factor Type 2 Receptor from Tupaia belangeri
TLDR
The tree shrew constitutes an important animal model in which to investigate the role of CRF receptor subtypes in the stress response and demonstrates that the CRF analogs urocortin and sauvagine bind with significantly greater affinity to these two CRF‐R2 splice variants than do human/rat and ovine CRF analogues.
Cloning of a splice variant of the pituitary adenylate cyclase-activating polypeptide (PACAP) type I receptor.
TLDR
Using RT-PCR, it is demonstrated the coexistence of a second form of mRNA, without this added insert, in DNAse-pretreated RNAs from both AR 4-2J cells and normal rat brain, indicating that common alternative splicing provokes the diversification of PACAP type I receptors into PACAPR1A (unspliced) and PAC APR1B (spliced) variants.
Cloning and Characterization of the Signal Transduction of Four Splice Variants of the Human Pituitary Adenylate Cyclase Activating Polypeptide Receptor
TLDR
Unlike the rat, PACAP binds and stimulates signal transduction with nearly equal affinity and potency for each of the receptor splice variants although with varying efficacy for the stimulation of phospholipase C in humans.
The amino-terminal fragment of the adenylate cyclase activating polypeptide (PACAP) receptor functions as a high affinity PACAP binding domain.
TLDR
The results suggest that the amino-terminus of the PACAP receptor functions as the major binding site for its ligand.
Identification of Amino Acids in the N‐Terminal Domain of Corticotropin‐Releasing Factor Receptor 1 that Are Important Determinants of High‐Affinity Ligand Binding
TLDR
Mutation of Arg76 or Asn81 but not Gly83 of hCRF‐R1 to the corresponding amino acids of xCRF-R1 or hVIP‐R2 resulted in 100‐1,000‐fold lower affinities for human/rat CRF, rat urocortin, and astressin.
Genomic Organization of the Rat Pituitary Adenylate Cyclase-activating Polypeptide Receptor Gene
TLDR
This study is the first to elucidate the structural organization of a PACAPR gene and to demonstrate that alternative splicing generates rPACAPR transcripts with unique 5′-UTRs.
The Genomic Structure of the Rat Corticotropin Releasing Factor Receptor
TLDR
Intron junctions were identified in the extracellular, transmembrane (TM), and cytoplasmic (C) domains of the CRFR, giving the potential for differential signal transduction by splice variants.
Cloning and functional characterization of a third pituitary adenylate cyclase-activating polypeptide receptor subtype expressed in insulin-secreting cells.
  • N. Inagaki, H. Yoshida, +5 authors S. Seino
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 1994
TLDR
The cloning, functional expression, and tissue distribution of a third PACAPR subtype are reported, suggesting that the diverse biological effects of PACAP are mediated by a family of structurally related proteins and thatPACAPR-3 participates in the regulation of insulin secretion.
The alternatively spliced type II corticotropin-releasing factor receptor, stably expressed in LLCPK-1 cells, is not well coupled to the G protein(s).
TLDR
Data indicate that the first cytoplasmic loop plays a crucial role in hCRF receptor coupling to the G protein, and indicates that CRF-RII is not well coupled to theG protein.
The Deletion of 14 Amino Acids in the Seventh Transmembrane Domain of a Naturally Occurring Calcitonin Receptor Isoform Alters Ligand Binding and Selectively Abolishes Coupling to Phospholipase C*
TLDR
Deletion of the residues in the seventh transmembrane domain in CTRΔe13 reduced the binding affinity for salmon and human calcitonin by more than 10-fold and approximately 2-fold, resulting in a receptor that failed to discriminate between the two forms of calcitonIn.
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