Identification of INSL5, a New Member of the Insulin Superfamily

Conklin, Darrell; Lofton–Day, Catherine; Haldeman, Betty A.; Ching, Andrew; Whitmore, Theodore E.; Lok, Si; Jaspers, Stephen R.

doi:10.1006/geno.1999.5899

Cited by 141 publications

(116 citation statements)

References 28 publications

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“…In recent years many new members of the relaxin/insulin/ IGF superfamily have been identified, either by differential cloning or by screening of the EST data bases using A-and B-chain motifs (20,21,38). The availability of the human genome sequence provides an ideal tool to screen for other novel relaxin genes.…”

Section: Discussionmentioning

confidence: 99%

“…All relaxins have a two-chain structure comprising an A-and Bpeptide chain linked by disulfide bonds with an intra-chain disulfide bond in the A-chain, analogous to that of insulin. Recently, two new insulin-like members of this peptide family have been identified in the expressed sequence tag (EST) data base (20,21). The availability of the human genome sequence provides a unique opportunity to discover other novel relaxin and relaxin-related genes.…”

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confidence: 99%

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Human Relaxin Gene 3 (H3) and the Equivalent Mouse Relaxin (M3) Gene

Bathgate

Samuel

Burazin

et al. 2002

Journal of Biological Chemistry

355

395

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We have identified a novel human relaxin gene, designated H3 relaxin, and an equivalent relaxin gene in the mouse from the Celera Genomics data base. Both genes encode a putative prohormone sequence incorporating the classic two-chain, three cysteine-bonded structure of the relaxin/insulin family and, importantly, contain the RXXXRXX(I/V) motif in the B-chain that is essential for relaxin receptor binding. A peptide derived from the likely proteolytic processing of the H3 relaxin prohormone sequence was synthesized and found to possess relaxin activity in bioassays utilizing the human monocytic cell line, THP-1, that expresses the relaxin receptor. The expression of this novel relaxin gene was studied in mouse tissues using RT-PCR, where transcripts were identified with a pattern of expression distinct from that of the previously characterized mouse relaxin. The highest levels of expression were found in the brain, whereas significant expression was also observed in the spleen, thymus, lung, and ovary. Northern blotting demonstrated an ϳ1.2-kb transcript present in mouse brain poly(A) RNA but not in other tissues. These data, together with the localization of transcripts in the pars ventromedialis of the dorsal tegmental nucleus of C57BLK6J mouse brain by in situ hybridization histochemistry, suggest a new role for relaxin in neuropeptide signaling processes. Together, these studies describe a third member of the human relaxin family and its equivalent in the mouse.Relaxin is a 6-kDa polypeptide hormone that is secreted by the ovary into the peripheral circulation in highest amounts during pregnancy and has a number of functions in mammals that are generally associated with female reproductive tract physiology (1). To date, only one relaxin gene has been characterized in most mammalian species, with the exception of the human where two separate genes have been described, designated H1 (2) and H2 (3) relaxin. The peptide encoded by the H2 gene is the major stored and circulating form in the human (4). H1 relaxin expression is restricted to the decidua, placenta, and prostate (5); however, the H1 peptide has similar biological activity to that of H2 relaxin in a rat atrial bioassay (6). The actions of relaxin include an ability to inhibit myometrial contractions, to stimulate remodeling of the connective tissue, and to induce softening of the tissues of the birth canal. Additionally, relaxin increases growth and differentiation of the mammary gland and nipple and induces the breakdown of collagen, one of the main components of connective tissue. Relaxin decreases collagen synthesis and increases the release of collagenases (7). These findings were recently confirmed by the establishment of the relaxin gene-knockout mouse (8), which exhibited a number of phenotypic properties associated with pregnancy. Female mice lacking a functionally active relaxin gene failed to relax and elongate the interpubic ligament of the pubic symphysis and could not suckle their pups, who in turn died within 24 h unless cross-fostered t...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Human Relaxin Gene 3 (H3) and the Equivalent Mouse Relaxin (M3) Gene

Bathgate

Samuel

Burazin

et al. 2002

Journal of Biological Chemistry

355

395

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“…Hence, insulinlike peptide-5 (INSL5) (Conklin et al, 1999;Hsu, 1999) and insulin-like peptide-6 (INSL6) (Hsu, 1999;Lok et al, 2000) were added to the relaxin peptide family (Fig. 2).…”

Section: Brief Historical Background Of Relaxin Family Peptides Anmentioning

confidence: 99%

International Union of Pharmacology LVII: Recommendations for the Nomenclature of Receptors for Relaxin Family Peptides

Bathgate

Ivell²,

Sanborn³

et al. 2006

Pharmacol Rev

288

256

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“…INSL5 is widely distributed with high expression in the gastrointestinal tract (Conklin et al, 1999) particularly in L cells isolated from mouse colon/rectum but also in ascending, transverse, and descending colon and proximal rectum, with lower levels in the cecum and distal rectum (Grosse et al, 2014). Low levels of Insl5 mRNA were found in the pancreas, thymus, and eye (Grosse et al, 2014).…”

Section: Introductionmentioning

confidence: 99%