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The ERBB2/HER2 receptor differentially interacts with ERBIN and PICK1 PSD-95/DLG/ZO-1 domain proteins

F Jaulin-Bastard1, H Saito, A Le Bivic

  • 1U119 INSERM, Molecular Oncology, Institut Paoli-Calmettes, 27 boulevard Leï Roure, 13009 Marseille, France.

The Journal of Biological Chemistry
|March 30, 2001
PubMed

Insights

New protein partners ERBIN and PICK1 bind to ERBB2/HER2 via PDZ domains, influencing receptor localization and clustering in epithelial cells. These interactions reveal novel regulatory mechanisms for ERBB2/HER2 signaling.

Area of Science:

  • Molecular and Cellular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • The ERBB2/HER2 receptor's activation and regulation are critical in normal physiology and disease.
  • Interactions with Src homology 2 (SH2) and phosphotyrosine binding (PTB) domain proteins are well-documented for ERBB2/HER2.

Purpose of the Study:

  • To identify novel protein partners of the ERBB2/HER2 receptor.
  • To elucidate the mechanisms by which these new partners interact with ERBB2/HER2 and influence its function.

Main Methods:

  • Co-immunoprecipitation assays to identify binding partners.
  • Analysis of protein-protein interactions using PDZ domain-mediated binding.
  • Investigation of protein localization and function in epithelial cells.

Main Results:

  • ERBIN and PICK1 were identified as new binding partners for ERBB2/HER2.
  • Both ERBIN and PICK1 associate with the carboxyl-terminal sequence of ERBB2/HER2 via a PDZ domain.
  • ERBIN appears to target ERBB2/HER2 to the basolateral epithelium, while PICK1 is implicated in receptor clustering.
  • ERBIN and PICK1 exhibit distinct binding mechanisms to ERBB2/HER2.

Conclusions:

  • ERBIN and PICK1 represent novel components of the ERBB2/HER2 signaling network.
  • The PDZ domain-mediated interactions contribute to ERBB2/HER2 localization and function.
  • These findings suggest complex regulatory mechanisms involving protein-protein interactions and potential oligomerization in ERBB2/HER2 specificity.

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