Biochemical analysis of the ligand for the neu oncogenic receptor

Y Yarden1, E Peles

  • 1Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.

Biochemistry
|April 9, 1991
PubMed

Insights

Researchers identified a 35-kDa glycoprotein ligand that stimulates the neu receptor (HER2). This factor also activates the epidermal growth factor (EGF) receptor, suggesting functional coupling between these key signaling molecules.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Oncology

Background:

  • The neu protooncogene (HER2/c-erbB2) encodes a cell-surface tyrosine kinase.
  • It is structurally related to the epidermal growth factor (EGF) receptor.
  • A candidate ligand for the neu receptor is secreted by ras-transformed fibroblasts.

Purpose of the Study:

  • To biochemically characterize the neu receptor stimulatory factor.
  • To investigate the functional relationship between the neu and EGF receptors.

Main Methods:

  • Partial purification using selective precipitation, heparin-agarose chromatography, and gel filtration.
  • Biochemical analyses of the ligand's properties (heat stability, sensitivity to reduction, precipitation).
  • Assays to test the ligand's activity on protooncogenic neu and EGF receptors.

Main Results:

  • The neu stimulatory factor is a 35-kDa glycoprotein, heat-stable but reduction-sensitive.
  • The partially purified ligand stimulated the protooncogenic neu receptor but not the constitutively active oncogenic neu protein.
  • The purified fraction also stimulated the EGF receptor, indicating potential functional coupling.

Conclusions:

  • The identified glycoprotein ligand plays a role in neu receptor activation.
  • Functional coupling or simultaneous interaction between neu and EGF receptors is suggested.
  • Further purification is needed to fully elucidate the ligand's mechanism of action.

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