High-level expression of TGF-beta 2 and the TGF-beta 2(414) precursor in Chinese hamster ovary cells

Growth Factors. 1990;3(2):129-38. doi: 10.3109/08977199009108275.

Abstract

Chinese hamster ovary (CHO) clones secreting high levels of transforming growth factor-beta 2 (TGF-beta 2) were obtained after transfection with a cDNA clone coding for the 414-amino acid TGF-beta 2 precursor and subsequent amplification with methotrexate. The TGF-beta 2 was secreted in a latent form since acidification was necessary for detection of maximal levels of bioactivity. Amino- and carboxy-terminal sequencing of purified recombinant TGF-beta 2 indicated that correct processing of mature TGF-beta 2 had occurred. In addition to mature TGF-beta 2, the recombinant CHO clones secreted larger proteins having molecular weights of 85, 105, and 130 kD, which consisted of both mature and pro-region sequences when analyzed by immunoblotting using site-specific anti-peptide antibodies. Analysis of serum- and cell-free media from recombinant CHO cells metabolically labeled with [3H]glucosamine and [32P]orthophosphate indicated that pro-TGF-beta 2 was glycosylated and phosphorylated. Two-dimensional electrophoretic analysis of acid hydrolysates showed that the 32P was incorporated into mannose-6-phosphate.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Chromatography, High Pressure Liquid
  • Cloning, Molecular
  • Cricetinae
  • Gene Expression Regulation*
  • Glycosylation
  • Hydrogen-Ion Concentration
  • Mannosephosphates / analysis
  • Methotrexate / pharmacology
  • Molecular Sequence Data
  • Molecular Weight
  • Phosphorylation
  • Protein Precursors / biosynthesis
  • Protein Precursors / genetics*
  • Protein Precursors / isolation & purification
  • Transfection
  • Transforming Growth Factor beta / biosynthesis
  • Transforming Growth Factor beta / genetics*
  • Transforming Growth Factor beta / isolation & purification

Substances

  • Mannosephosphates
  • Protein Precursors
  • Transforming Growth Factor beta
  • mannose-6-phosphate
  • Methotrexate