Vr. Fantin et al., Cloning, tissue expression, and chromosomal location of the mouse insulin receptor substrate 4 gene, ENDOCRINOL, 140(3), 1999, pp. 1329-1337
The insulin receptor substrates (IRSs) are key proteins in signal transduct
ion from the insulin receptor. Recently, we discovered a fourth member of t
his family, designated IRS-4, cloned its complementary DNA from the human e
mbryonic kidney 293 cell Line, and characterized its signaling properties i
n 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 gen
es for IRS-1 and -2. The predicted amino acid sequence of mouse IRS-I is hi
ghly homologous with that of human IRS-4; the pleckstrin homology domain, t
he phosphotyrosine-binding domain, and the tyrosine phosphorylation motifs
are especially well conserved. The tissue distribution of IRS-4 in the mous
e was determined by analysis for the expression of its messenger RNA by RT-
PCR and for the protein itself by immunoprecipitation and immunoblotting. T
he messenger RNA was detected in skeletal muscle, brain, heart, kidney, and
liver, but the protein itself was not detected in any tissue. These result
s 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 backcross
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.