Cloning and increased expression of an insulin receptor substrate-1-like gene in human hepatocellular carcinoma.
Human insulin receptor substrate-1 (hIRS-1) cDNAs were cloned from a lambda GT11 expression library using a monoclonal antibody (MAb) produced against a human hepatocellular carcinoma (HCC) cell line (FOCUS). The predicted amino acid sequence derived from both a genomic DNA fragment and the cDNAs showed a 90.5% identity to the previously reported rat IRS-1 cDNA [Sun, X.P. (1991) Nature 352, 73-77]. Multiple potential phosphorylation sites, that suggest an intrinsic function of this molecule in response to insulin action, were highly conserved between the two species. A c.a. 180 kDa hIRS-1 protein was immunoprecipitated and found to be phosphorylated on tyrosine residue(s) following insulin stimulation of HuH-7 HCC cells. Northern blot analysis demonstrated a single c.a. 5 kb transcript in HCC cell lines and tissues. Higher levels of hIRS-1 gene transcripts were observed in HCC tumors compared to adjacent non-involved normal liver.
Nishiyama
M
M
Molecular Hepatology Laboratory, Massachusetts General Hospital Cancer Center, Boston.
Wands
J R
JR
D000595:Amino Acid Sequence; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D015870:Gene Expression; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D008113:Liver Neoplasms / Q000235:genetics*; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics*; D011993:Recombinant Fusion Proteins; D012689:Sequence Homology, Nucleic Acid
C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins