Functional Analysis of the ErbB4 Receptor Tyrosine Kinase

Abstract

ErbB4 is a member of the signaling network composed of the EGF (epidermal growth factor) family of peptide hormones and the ErbB family of receptor tyrosine kinases. We have hypothesized that ErbB4 is a mammary-specific tumor suppressor. Indeed, we have preliminary data that indicates that overexpression of ErbB4 causes the EGF family hormones EGF and Neuregulin to inhibit DNA synthesis of a human mammary tumor cell line. Furthermore, we have constructed three constitutively active, ligand-independent ErbB4 mutants. We have published data indicating that these mutants do not malignantly transform the growth of cultured rodent fibroblasts. These data indicate that ErbB4 is not an oncogene. Moreover, we have preliminary data indicating that one of the three constitutively active ErbB4 mutants inhibits proliferation of several human mammary cell lines. Analyses of additional ErbB4 mutants suggest that this growth inhibition is dependent on ErbB4 kinase activity and on phosphorylation of tyrosine 1056 in the carboxyl-terminal region of the ErbB4 cytoplasmic domain.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2003
Accession Number
ADA418035

Entities

People

  • David J. Riese

Organizations

  • Purdue Research Foundation

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Breast Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Culture Media
  • Epithelial Cells
  • Fibroblasts
  • Health Services
  • Proteins
  • Tumor Cell Line
  • Tyrosine

Fields of Study

  • Biology
  • Computer science

Readers

  • Breast cancer cell signaling and growth regulation.