Characterization of a natural inhibitor of the insulin receptor tyrosine kinase: cDNA cloning, purification, and anti-mitogenic activity

Cell. 1989 Aug 25;58(4):631-40. doi: 10.1016/0092-8674(89)90098-6.

Abstract

Amino acid sequence of the precursor of the phosphorylated N-glycoprotein (pp63) secreted by rat hepatocytes was deduced from the cDNA sequence. This polypeptide (Mr = 40,586) was rich in both cysteine and proline and contained three potential N-glycosylation sites. A single pp63 mRNA species (approximately 2000 bp), found in normal hepatocytes but not in FaO hepatoma cells, appeared to result from transcription of a single gene. pp63 purified by affinity chromatography inhibited insulin receptor tyrosine kinase and receptor autophosphorylation. Only the phosphorylated form of the protein was active. In additon, pp63 antagonized the growth-promoting action of insulin in FaO cells but did not affect hormone-mediated increase in amino acid transport capacity or tyrosine aminotransferase induction in these cells.

MeSH terms

  • Acute-Phase Proteins*
  • Amino Acid Sequence
  • Amino Acids / metabolism
  • Animals
  • Base Sequence
  • Cell Division / drug effects
  • Cloning, Molecular
  • DNA / genetics
  • Glycoproteins / genetics
  • Glycoproteins / isolation & purification
  • Insulin Antagonists / genetics
  • Insulin Antagonists / isolation & purification
  • Insulin Antagonists / pharmacology
  • Liver Neoplasms, Experimental
  • Molecular Sequence Data
  • Phosphoproteins / genetics*
  • Phosphoproteins / isolation & purification
  • Phosphoproteins / pharmacology
  • Phosphorylation
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Rats
  • Receptor, Insulin / antagonists & inhibitors*

Substances

  • Acute-Phase Proteins
  • Amino Acids
  • Glycoproteins
  • Insulin Antagonists
  • Phosphoproteins
  • acute-phase phosphoprotein pp63
  • DNA
  • Protein-Tyrosine Kinases
  • Receptor, Insulin

Associated data

  • GENBANK/M29758