Alternative splicing, gene localization, and binding of SH2-B to the insulin receptor kinase domain

The SH2-B protein is an SH2-domain-containing molecule that interacts with a number of phosphorylated kinase and receptor molecules including the insu lin receptor. Two isoforms of the SH2-B have been identified and have been proposed to arise through alternate splicing. Here we have identified a thi rd isoform of the SH2-B protein, SH2-B gamma, that interacts specifically w ith the insulin receptor. This interaction required phosphorylation of resi due Y1146 in the triple tyrosine motif within the activation loop of the IR kinase and is one of only two signaling molecules shown to interact direct ly with this residue of the insulin receptor kinase domain. The intron/exon structure of the SH2-B gene was determined. Alternate splice sites utilize d to generate the different isoforms of the SH2-B protein were identified i n the 3' end of the SH2-B gene immediately downstream of the exon encoding the core of the SH2 domain. Additionally, the chromosomal location of the S H2-B gene was determined to be the distal arm of mouse Chromosome (Chr) 7 i n a region linked to obesity in mice.