PMID- 10067860 OWN - NLM STAT- MEDLINE DCOM- 19990323 LR - 20081121 IS - 0013-7227 (Print) IS - 0013-7227 (Linking) VI - 140 IP - 3 DP - 1999 Mar TI - Cloning, tissue expression, and chromosomal location of the mouse insulin receptor substrate 4 gene. PG - 1329-37 AB - The insulin receptor substrates (IRSs) are key proteins in signal transduction from the insulin receptor. Recently, we discovered a fourth member of this family, designated IRS-4, cloned its complementary DNA from the human embryonic kidney 293 cell line, and characterized its signaling properties in this cell line. As part of an investigation of the physiological role of this IRS, we have now cloned the mouse IRS-4 gene and determined its tissue expression and chromosomal location. The coding region of the mouse IRS-4 gene contains no introns, and in this regard is the same as that of the genes for IRS-1 and -2. The predicted amino acid sequence of mouse IRS-4 is highly homologous with that of human IRS-4; the pleckstrin homology domain, the phosphotyrosine-binding domain, and the tyrosine phosphorylation motifs are especially well conserved. The tissue distribution of IRS-4 in the mouse was determined by analysis for the expression of its messenger RNA by RT-PCR and for the protein itself by immunoprecipitation and immunoblotting. The messenger RNA was detected in skeletal muscle, brain, heart, kidney, and liver, but the protein itself was not detected in any tissue. These results indicate that IRS-4 is a very rare protein. The chromosomal locations of the mouse IRS-4 and IRS-3 genes were determined by interspecific back-cross analysis and were found to be on chromosomes X and 5, respectively. As the mouse genes for IRS-1 and -2 are on chromosomes 1 and 8, respectively, each IRS gene resides on a different chromosome. FAU - Fantin, V R AU - Fantin VR AD - Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA. FAU - Lavan, B E AU - Lavan BE FAU - Wang, Q AU - Wang Q FAU - Jenkins, N A AU - Jenkins NA FAU - Gilbert, D J AU - Gilbert DJ FAU - Copeland, N G AU - Copeland NG FAU - Keller, S R AU - Keller SR FAU - Lienhard, G E AU - Lienhard GE LA - eng GR - DK-42816/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Endocrinology JT - Endocrinology JID - 0375040 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (IRS4 protein, human) RN - 0 (Insulin Receptor Substrate Proteins) RN - 0 (Irs4 protein, mouse) RN - 0 (Phosphoproteins) SB - IM MH - Adaptor Proteins, Signal Transducing MH - Amino Acid Sequence MH - Animals MH - Base Sequence MH - Cell Line MH - *Chromosome Mapping MH - Cloning, Molecular MH - Embryonic and Fetal Development/physiology MH - Gene Expression Regulation/*physiology MH - Humans MH - Insulin Receptor Substrate Proteins MH - Mice MH - Molecular Sequence Data MH - Phosphoproteins/*genetics MH - Reverse Transcriptase Polymerase Chain Reaction MH - Sequence Homology, Amino Acid EDAT- 1999/03/06 00:00 MHDA- 1999/03/06 00:01 CRDT- 1999/03/06 00:00 PHST- 1999/03/06 00:00 [pubmed] PHST- 1999/03/06 00:01 [medline] PHST- 1999/03/06 00:00 [entrez] AID - 10.1210/endo.140.3.6578 [doi] PST - ppublish SO - Endocrinology. 1999 Mar;140(3):1329-37. doi: 10.1210/endo.140.3.6578.