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Related Experiment Videos

The transmembrane heregulin precursor is functionally active.

Z Aguilar1, D J Slamon

  • 1Department of Medicine, Division of Hematology/Oncology, UCLA School of Medicine, Los Angeles, California 90024, USA.

The Journal of Biological Chemistry
|August 10, 2001
PubMed
Summary
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Membrane-anchored heregulin (HRG) is biologically active, binding to HER-3 receptors and activating signaling pathways. This study shows transmembrane HRG plays a role in cell-cell communication and signal transduction.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Eukaryotic polypeptide growth factors are often synthesized as transmembrane precursors.
  • Some membrane-bound growth factor precursors exhibit biological activity, suggesting roles in cell-cell communication.
  • Secreted heregulin (HRG) is a growth factor homologous to epidermal growth factor (EGF).

Purpose of the Study:

  • To evaluate the biological activity of plasma membrane-anchored heregulin in human breast cells.
  • To investigate the role of transmembrane heregulin in cell-cell communication and signal transduction.

Main Methods:

  • Assessing the binding of transmembrane heregulin to cells expressing HER-3.
  • Measuring the phosphorylation of p185(HER-2/neu) in response to transmembrane heregulin.

Related Experiment Videos

  • Evaluating DNA synthesis in cells overexpressing HER-2/neu.
  • Co-culturing heregulin-producing cells with cells expressing heregulin receptors to observe in vivo associations.

    • Main Results:

    • Transmembrane heregulin binds to cells expressing p180(HER-3).
    • Heregulin binding induces p185(HER-2/neu) phosphorylation and increases DNA synthesis.
    • Specific in vivo associations were observed when heregulin-producing cells were co-cultured with receptor-bearing cells.

    Conclusions:

    • Transmembrane heregulin is functionally active.
    • Membrane-anchored heregulin can play a role in cell-cell communication.
    • Transmembrane heregulin is involved in subsequent signal transduction in vivo.