Cloning, tissue expression, and chromosomal localization of the mouse IRS-3 gene.
Insulin receptor substrate (IRS) proteins are key regulators of basic functions such as cellular growth and metabolism. They provide an interface between multiple receptors and a complex network of intracellular signaling molecules. Two members of this family (IRS-1 and IRS-2) have been identified previously. In this investigation, we analyzed a mouse expressed sequence tag clone that proved to be a new member of the IRS family. Sequence analysis of this clone and comparison with the sequences deposited in GenBank demonstrates this protein may be the murine homolog of rat IRS-3, recently purified and cloned from rat adipocytes. Accordingly, we have named our protein mouse IRS-3. The expressed sequence tag clone contains the complete coding sequence of 1485 bp, encoding a protein of 495 amino acids. Sequence alignment with the other members of the IRS family shows that this protein contains pleckstrin homology and phosphotyrosine-binding domains that are highly conserved. In addition, there is conservation of many tyrosine phosphorylation motifs responsible for interactions with downstream signaling molecules containing SH2 domains. The murine IRS-3 messenger RNA (2.4 kilobases in length) is expressed in many tissues, with highest levels in liver and lung. Mouse IRS-3 is highly expressed in the first part of the embryonic life, when IRS-1 messenger RNA is barely detectable. Unlike the genes encoding IRS-1 and IRS-2, the IRS-3 gene contains an intron (344 bp in length) in the region between the pleckstrin homology and the phosphotyrosine-binding domains. Fluorescent in situ hybridization localized the mouse IRS-3 gene on the telomeric region of chromosome 5G2. Cloning of the murine IRS-3 gene will make it possible to apply genetic approaches to elucidate the physiological role of this new member of the IRS family of proteins.
Sciacchitano
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Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1829, USA.
Taylor
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D016678:Genome; D055504:Insulin Receptor Substrate Proteins; D051379:Mice / Q000235:genetics*; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics*; D051381:Rats / Q000235:genetics; D016415:Sequence Alignment; D014018:Tissue Distribution
D018076:DNA, Complementary; D055504:Insulin Receptor Substrate Proteins; C108872:Irs3 protein, mouse; C491584:Irs3 protein, rat; D010750:Phosphoproteins