IMR Press / FBL / Volume 7 / Issue 4 / DOI: 10.2741/grant

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Article
Roles of ERBB family receptor tyrosine kinases, and downstream signaling pathways, in the control of cell growth and survival
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1 Department of Radiation Oncology, Medical College of Virginia,Virginia Commonwealth University, Richmond VA 23298-0058, USA
2 Department of Hematology/Oncology, Medical College of Virginia,Virginia Commonwealth University, Richmond VA 23298-0058, USA
3 Departments of Pharmacology and Toxicology, Medical College of Virginia,Virginia Commonwealth University, Richmond VA 23298-0058, USA
Front. Biosci. (Landmark Ed) 2002, 7(4), 376–389; https://doi.org/10.2741/grant
Published: 1 February 2002
Abstract

Within the last 20 years, multiple novel intracellular signal transduction pathways, downstream of plasma membrane receptors, have been discovered. These pathways have been linked to the regulation of diverse cellular events such as proliferation, senescence, differentiation and apoptosis. This review will focus upon the roles of signaling by the ErbB receptor tyrosine kinase family (ErbB1-4) in the survival of cells in response to cytotoxic stresses. In addition, plasma membrane-to-nucleus signaling pathways downstream of these receptors, such as mitogen activated protein kinase (MAPK) and phosphatidyl inositol 3-kinase (PI3K), in the control of cell survival will be discussed. Recent evidence suggests that signaling by the MAPK and PI3K pathways can both enhance proliferation as well as protect cells from apoptosis. We describe potential mechanisms by which modulation of pathway activities following inhibition of ErbB receptor function may alter the sensitivity of cells to toxic insults, leading to increased apoptosis and loss of clonogenic survival.

Keywords
Signal Transduction
Cell Cycle
ErbB1
EGF receptor
ErbB2
Tyrphostin
Mitogen Activated Protein Kinase (MAPK)
c-Jun NH2 -terminal kinase (JNK)
Phosphatidyl Inositol 3-kinase (PI3K)
Cyclin Kinase Inhibitor Protein (CKI)
p21Cip-1/WAF1/mda6
Apoptosis
Caspase
Mitochondria
Review
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