Disease relevance of SCTR

• The high receptor expression in cholangiocarcinomas may be used for in vivo secretin receptor-targeting of these tumors and for the differential diagnosis with hepatocellular carcinoma [1].
• The secretin receptor expression was investigated in the human liver because the liver is a physiological secretin target and because novel diagnostic and treatment modalities are needed for liver cancer [1].
• METHODS: Nineteen normal livers, 10 cirrhotic livers, 35 cholangiocarcinomas, and 45 hepatocellular carcinomas were investigated for secretin receptor expression by in vitro receptor autoradiography using (125)I-[Tyr(10)] rat secretin and, in selected cases, for secretin receptor mRNA by RT-PCR [1].
• A cDNA encoding the human secretin receptor was isolated from a human pancreatic adenocarcinoma cell-line cDNA library using polymerase chain reaction and library screening techniques [2].
• RESULTS: We confirmed the molecular nature of the secretin receptor in the gastrinomas with a positive provocative test result and identified a novel mechanism for a false-negative result [3].
• Secretin-receptor mRNA was detectible in all gastrinomas but varied 132-fold with a mean of 0.89 +/- 0.12 molecules per beta-actin [4].
• Each of 9 pancreatic cancer specimens and no normal tissue expressed a secretin receptor variant with exons 3 and 4 deleted [5].

High impact information on SCTR

• Tumor expression of the class B G protein-coupled secretin receptor mediates a positive result [3].
• The secretin receptor resembles that of the pancreatic D cells and acts through increasing intracellular cyclic adenosine monophosphate levels [6].
• This spliceoform has only recently been recognized in a rare gastrinoma, where it was incapable of binding secretin or signaling, and possessed dominant-negative activity to suppress hormone action at the wild-type secretin receptor (1) [7].
• Here, we examine the possible presence and function of molecular forms of the secretin receptor in pancreatic cancer cell lines and in primary tumors [7].
• Silencing of secretin receptor function by dimerization with a misspliced variant secretin receptor in ductal pancreatic adenocarcinoma [7].

Chemical compound and disease context of SCTR

• We studied gastrinoma cells in vitro to determine whether secretin would stimulate gastrin release directly and whether the gastrinoma cell membrane had a functional secretin receptor adenylate cyclase system [8].

Biological context of SCTR

• Immunoprecipitation of a functional, N-terminal epitope-tagged secretin receptor was used to demonstrate agonist-dependent receptor phosphorylation, with an EC50 of 14 nM [9].
• CpG methylation and transcription factors Sp1 and Sp3 regulate the expression of the human secretin receptor gene [10].
• Role of N-linked glycosylation on the function and expression of the human secretin receptor [11].
• Localization of the gene encoding the secretin receptor, SCTR, on human chromosome 2q14.1 by fluorescence in situ hybridization and chromosome morphometry [12].
• In this work, we utilized hybridization screening of a human pancreatic cDNA library to clone a 1.8-kb cDNA encoding a 440 amino acid protein 81% identical to the rat pancreatic secretin receptor [13].

Anatomical context of SCTR

• COS-7 cells transfected with this cDNA bound secretin with a high affinity, and vasoactive intestinal peptide with a lower affinity, appropriate for a secretin receptor [13].
• Secretin mRNAs are found in Purkinje cells whereas secretin receptor transcripts are present in Purkinje cells and basket cells in the molecular cell layer [14].
• Thus, like the AT(1A)R, secretin receptor internalization is not inhibited by reagents that interfere with clathrin-coated vesicle-mediated internalization and in accordance with these results, we show that secretin and AT(1A) receptors colocalize in endocytic vesicles [15].
• To functionally characterize the receptor and evaluate its signal transduction pathway, the full-length human secretin receptor cDNA was subcloned into the mammalian expression vector pRc/CMV and expressed in cultured CHO cells [16].
• Interestingly, the transcripts for secretin receptor were also detected in the epicardium and myocardium of the developing heart as well as the glomerulus and collecting duct in the developing kidney [17].

Associations of SCTR with chemical compounds

• The secretin receptor was regulated by guanine nucleotides, with guanosine 5'-(beta, gamma-imino)-triphosphate being the most potent to accelerate the rate of dissociation of bound secretin [18].
• Human secretin receptor is a G protein-coupled receptor that is functionally linked to the cAMP second messenger system by stimulation of adenylate cyclase [16].
• Lysine 173 residue within the first exoloop of rat secretin receptor is involved in carboxylate moiety recognition of Asp 3 in secretin [19].
• There is a large family of G-protein-coupled receptors, including 874 rhodopsin-type receptors, 28 metabotropic glutamate-like receptors and a remarkably expanded group of 161 secretin receptor-like proteins [20].

Physical interactions of SCTR

• A role for receptor kinases in the regulation of class II G protein-coupled receptors. Phosphorylation and desensitization of the secretin receptor [9].

Other interactions of SCTR

• We report here the isolation of a 1616-base pair cDNA from human lung tissue that encodes a 440-amino acid, 50-kDa, G protein-coupled human secretin receptor (HSR), with homology of 80% with the rat secretin receptor and 37% with the human type I vasoactive intestinal peptide receptor [21].
• The cytoplasmic tails of the secretin receptor and the growth hormone releasing hormone receptor either interact poorly or not at all with calmodulin, respectively [22].
• Two very informative chimeras respectively referred to as S144V and S123V were obtained by replacing the entire ectodomain or only the first 123 amino acids of the VPAC1 receptor by the corresponding sequences of the secretin receptor [23].
• Structure of the human CD97 gene: exon shuffling has generated a new type of seven-span transmembrane molecule related to the secretin receptor superfamily [24].
• Charged residues that are conserved in the TM regions of most or all members of the PTH/secretin receptor subfamily were targeted [25].

Analytical, diagnostic and therapeutic context of SCTR

• Molecular cloning and expression of a human secretin receptor [21].
• In this paper we characterize the internalization of a wild-type and carboxyl-terminal (COOH-terminal) truncated secretin receptor using flow cytometry and fluorescence imaging, and compare the properties of secretin receptor internalization to that of the beta(2)-AR [15].

References