Cloning of the chicken insulin receptor substrate 1 gene.
The action of insulin, IGF-1, and IGF-2 is mediated via two receptor tyrosine kinases, the insulin and IGF-1 receptors. Upon ligand binding, these receptors become active kinases, undergoing autophosphorylation and phosphorylating cellular substrates, including insulin receptor substrate-1 (IRS-1). IRS-1 acts as a docking protein and mediates multiple interactions among other proteins, resulting in transduction of the metabolic and mitogenic signals. The IRS-1 gene has been cloned from four species (human, rat, mouse, and frog). In the present study, the chicken IRS-1 gene was cloned. Chicken, as is true of birds in general, have a higher fasting and fed blood glucose than do mammals. Chicken IRS-1 DNA sequence encodes a 1240 amino acid protein. The most conserved regions were the IRS homology-2 (IH-2), the pleckstrin homology, and the shc and IRS-1 NPXY-binding (SAIN) domains. Twelve of the cIRS-1 tyrosine residues are in sequence motifs that, when phosphorylated, could interact with proteins containing SH2 domains. All twelve of these motifs were conserved. IRS-1 mRNA is expressed during embryogenesis in chicken and persists after hatching. In LMH cells, derived from a chicken hepatoma, two bands were tyrosine phosphorylated in an insulin-dependent manner: IRS-1 (approximately 180 kDa) and the insulin receptor beta subunit (approximately 95 kDa). Chicken IRS-1 is structurally and functionally similar to its human homolog, despite the difference in blood glucose levels and the evolutionary distance between birds and mammals.
Taouis
M
M
Institut National de la Recherche Agronomique, Station de Recherches Avicoles, Nouzilly, France.
Taylor
S I
SI
Reitman
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D001001:Anura; D002642:Chick Embryo; D003001:Cloning, Molecular; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins; D051379:Mice; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D000906:Antibodies; C526292:IRS1 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; C526296:Irs1 protein, rat; D010750:Phosphoproteins; D014443:Tyrosine; D011972:Receptor, Insulin