Distinctive tissue distribution and phosphorylation of IRSp53 isoforms.
An insulin-receptor substrate of 53-kDa protein (IRSp53) is an adapter protein, which interacts with the Rho-family of GTPases and mediates neurite outgrowth. It also binds to DRPLA protein, a product of the gene responsible for a polyglutamine disease, dentatorubral-pallidoluysian atrophy (DRPLA). Isoforms of human IRSp53 have been reported, each with a unique amino acid sequence at the C-terminal end. Here we report the distinctive tissue distribution and phosphorylation of three isoforms (L, S, and T-forms). Western blotting analyses with isoform-specific antibodies demonstrated that the L and S-forms were expressed in the brain, whereas the T-form was not present in any tissues examined, but was found in a cancer cell line. The L and S-forms were phosphorylated upon stimulation with insulin, and the T-form with IGF-I. Since phospho-acceptor sites were localized to the common portion, the difference in phosphorylation seems to be due to the unique C-terminal sequence.
Okamura-Oho
Y
Y
Department of Genetics, National Children's Medical Research Center, 3-35-31 Taishido, Setagaya, Tokyo, 154-8509, Japan.
Miyashita
T
T
Yamada
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D007120:Immunochemistry; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D014443:Tyrosine / Q000737:chemistry
C119539:BAIAP2 protein, human; D007328:Insulin; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D011994:Recombinant Proteins; C095278:atrophin-1; D014443:Tyrosine; D007334:Insulin-Like Growth Factor I