Intermolecular association of the p185neu protein and EGF receptor modulates EGF receptor function

Cell. 1990 Jun 29;61(7):1339-47. doi: 10.1016/0092-8674(90)90697-d.

Abstract

We have used cross-linking reagents on cell lines expressing both p185neu and EGFR. The lysates of the cells were precipitated with anti-p185neu or anti-EGFR antibodies. These precipitates included a high molecular weight complex that was identified as an EGFR-p185neu heterodimer. Heterodimerization was found to be induced by exposure to EGR. The EGFR of these cells displayed three affinity states for EGF: low (Kd, approximately 10(-9) M), high (Kd, 10(-9) to 10(-10) M), and very high (Kd, 10(-11) M), as determined by Scatchard analyses. Relatively small levels of EGF had a dramatic biological effect on cells expressing very high affinity EGFR. The very high affinity EGFR disappeared after the cells were treated with anti-p185neu monoclonal antibodies that selectively down-regulated p185neu. EGF and TPA had differential effects on down-modulation of the EGFR in cells that express either one or both species of receptor proteins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Division
  • Cell Line
  • Cell Transformation, Neoplastic*
  • Cross-Linking Reagents
  • DNA Replication
  • Down-Regulation / drug effects
  • Epidermal Growth Factor / metabolism
  • Epidermal Growth Factor / pharmacology
  • ErbB Receptors / drug effects
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Fibroblasts / metabolism
  • Gene Expression
  • Kinetics
  • Macromolecular Substances
  • Mice
  • Molecular Weight
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogenes
  • Receptor, ErbB-2
  • Tetradecanoylphorbol Acetate / pharmacology
  • Thymidine / metabolism

Substances

  • Cross-Linking Reagents
  • Macromolecular Substances
  • Proto-Oncogene Proteins
  • Epidermal Growth Factor
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • Receptor, ErbB-2
  • Tetradecanoylphorbol Acetate
  • Thymidine