Endocrine-Related Cancer (2001) 8 151–159 The ErbB receptor tyrosine family as signal integrators N E Hynes, K Horsch, M A Olayioye and A Badache Friedrich Miescher Institute, PO Box 2543, CH-4002 Basel, Switzerland (Requests for offprints should be addressed to N E Hynes, Friedrich Miescher Institute, R-1066.206, Maulbeerstrasse 66, CH-4058 Basel, Switzerland. Email:
[email protected]) (M A Olayioye is now at The Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Victoria 3050, Australia) Abstract ErbB receptor tyrosine kinases (RTKs) and their ligands have important roles in normal development and in human cancer. Among the ErbB receptors only ErbB2 has no direct ligand; however, ErbB2 acts as a co-receptor for the other family members, promoting high affinity ligand binding and enhancement of ligand-induced biological responses. These characteristics demonstrate the central role of ErbB2 in the receptor family, which likely explains why it is involved in the development of many human malignancies, including breast cancer. ErbB RTKs also function as signal integrators, cross-regulating different classes of membrane receptors including receptors of the cytokine family. Cross-regulation of ErbB RTKs and cytokines receptors represents another mechanism for controlling and enhancing tumor cell proliferation. Endocrine-Related Cancer (2001) 8 151–159 Introduction The EGF-related peptide growth factors The epidermal growth factor (EGF) or ErbB family of type ErbB receptors are activated by ligands, known as the I receptor tyrosine kinases (RTKs) has four members:EGF EGF-related peptide growth factors (reviewed in Peles & receptor, also termed ErbB1/HER1, ErbB2/Neu/HER2, Yarden 1993, Riese & Stern 1998).