Ligand-independent oncogenic signaling by the epidermal growth factor receptor: v-ErbB as a paradigm

Julie L. Boerner, Andrew Danielsen, Nita Jane Maihle

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Relay of information from the extracellular environment into the cell often results from a peptide growth factor binding to its cognate cell surface receptor this event is an integral mechanism by which many cellular functions occur, including cell growth, motility, and survival. In recent years, however, this requirement for ligand binding has been shown to be surpassed by several distinct mechanisms, including cell surface receptor crosstalk (e.g., between epidermal growth factor receptor [EGFR] and G-coupled receptors), receptor-extracellular matrix interactions (e.g., EGFR: integrin complexes), and finally by structural mutations within the receptor itself. While all of these pathways result in so-called ligand-independent signaling by the EGF receptor, to date, only structural mutations in the receptor have been shown to result in qualitative changes in downstream targets of the receptor, which specifically result in oncogenic signaling, transformation, and tumorigenicity. In this review, we describe aspects of the known signaling properties of the retroviral oncogene v-ErbB as a model of ligand-independent oncogenic signaling, and compare these properties to results emerging from ongoing studies on structurally related EGF receptor mutants originally identified in human tumors. A better understanding of the signaling pathways used by these uniquely oncogenic receptor tyrosine kinase mutants may ultimately reveal new targets for the development of novel therapeutics selective for the inhibition of tumor cell growth.

Original languageEnglish (US)
Title of host publicationThe EGF Receptor Family
Subtitle of host publicationBiologic Mechanisms and Role in Cancer
PublisherElsevier Inc.
Pages115-125
Number of pages11
ISBN (Electronic)9780080472584
ISBN (Print)9780121602819
DOIs
StatePublished - Dec 19 2003

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Keywords

  • Caldesmon
  • Cancer
  • EGF receptor
  • ErbB
  • Ligand-independent signaling
  • Oncogenes
  • Oncogenic signaling
  • Pak
  • Receptor tyrosine kinase
  • v-ErbB

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Boerner, J. L., Danielsen, A., & Maihle, N. J. (2003). Ligand-independent oncogenic signaling by the epidermal growth factor receptor: v-ErbB as a paradigm. In The EGF Receptor Family: Biologic Mechanisms and Role in Cancer (pp. 115-125). Elsevier Inc.. https://doi.org/10.1016/B978-012160281-9/50010-4