ErbB4/HER4: Role in Mammary Gland Development, Differentiation and Growth Inhibition

  • Rebecca S. Muraoka-Cook
  • Shu-Mang Feng
  • Karen E. Strunk
  • H. Shelton EarpIIIEmail author


The ErbB receptor tyrosine kinase family has often been associated with increased growth of breast epithelial cells, as well as malignant transformation and progression. In contrast, ErbB4/HER4 exhibits unique attributes from a two step proteolytic cleavage which releases an 80 kilodalton, nuclear localizing, tyrosine kinase to a signal transduction mechanism that slows growth and stimulates differentiation of breast cells. This review provides an overview of ErbB4/HER4 in growth and differentiation of the mammary epithelium, including its physiologic role in development, the contrasting growth inhibition/tumor suppression and growth acceleration of distinct ErbB4/HER4 isoforms and a description of the unique cell cycle regulated pattern of nuclear HER4 ubiquitination and destruction.


Mammary development Growth inhibition HER4 and breast cancer 



epidermal growth factor


epidermal growth factor receptor




receptor tyrosine kinase


heparin binding epidermal growth factor-like factor


tumor necrosis factor-alpha converting enzyme


GFP tagged HER4 C-terminus w/o the tyrosine kinase domain




terminal end buds




mammary epithelial cells


Janus kinase 2


signal transducer and transcriptional activator 5a


anaphase promoting complex/cyclosome


hyperplastic alveolar nodules


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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Rebecca S. Muraoka-Cook
    • 1
    • 2
  • Shu-Mang Feng
    • 1
  • Karen E. Strunk
    • 1
  • H. Shelton EarpIII
    • 1
    • 3
    • 4
    Email author
  1. 1.UNC-Lineberger Comprehensive Cancer CenterUniversity of North Carolina Chapel HillChapel HillUSA
  2. 2.Department of GeneticsUniversity of North Carolina School of MedicineChapel HillUSA
  3. 3.Department of MedicineUniversity of North Carolina School of MedicineChapel HillUSA
  4. 4.Department of PharmacologyUniversity of North Carolina School of MedicineChapel HillUSA

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