TY - JOUR
T1 - Ligand-independent oncogenic signaling by the epidermal growth factor receptor
T2 - v-ErbB as a paradigm
AU - Boerner, Julie L.
AU - Danielsen, Andrew
AU - Maihle, Nita J.
N1 - Funding Information:
The authors gratefully acknowledge the assistance of Ms. Courtney Lovejoy and Ms. Sharon Jones in the preparation of this manuscript. This study has been supported by the NIH (CA 79808).
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2003/3/10
Y1 - 2003/3/10
N2 - 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 cross-talk (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.
AB - 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 cross-talk (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.
KW - Caldesmon
KW - Cancer
KW - EGF receptor
KW - ErbB
KW - Ligand-independent signaling
KW - Oncogenes
KW - Oncogenic signaling
KW - Pak
KW - Receptor tyrosine kinase
KW - v-ErbB
UR - http://www.scopus.com/inward/record.url?scp=0037429728&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037429728&partnerID=8YFLogxK
U2 - 10.1016/S0014-4827(02)00096-4
DO - 10.1016/S0014-4827(02)00096-4
M3 - Review article
C2 - 12648470
AN - SCOPUS:0037429728
SN - 0014-4827
VL - 284
SP - 111
EP - 121
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 1
ER -