Roles of ERBB family receptor tyrosine kinases, and downstream signaling pathways, in the control of cell growth and survival.
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.
Grant
Steven
S
Department of Hematology/Oncology, Medical College of Virginia,Virginia Commonwealth University, Richmond, VA 23298-0058, USA.
Qiao
Liang
L
Dent
Paul
P
D000818:Animals; D020169:Caspases / Q000378:metabolism; D002455:Cell Division; D002470:Cell Survival; D066246:ErbB Receptors / Q000502:physiology; D020935:MAP Kinase Signaling System; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000502:physiology; D020893:Receptor, ErbB-3 / Q000502:physiology; D066247:Receptor, ErbB-4; D015398:Signal Transduction
D020169:Caspases; D066246:ErbB Receptors; D019869:Phosphatidylinositol 3-Kinases; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4