The ErbB (Erythroblastic Leukemia Viral Oncogene Homolog) family of transmembrane RTKs (Receptor Tyrosine Kinases) plays an important role in the pathogenesis of many cancers (Ref.1). This family is comprised of four members EGFR (Epidermal Growth Factor Receptor), ErbB2, ErbB3, and ErbB4 (Ref.2). ErbB2 also called Her2 (Heregulin-2) and ErbB3 are closely related to the EGFR/ErbB1, but unlike EGFR, ErbB2 is a ligandless receptor, whereas ErbB3 lacks tyrosine kinase activity. Hence, both ErbB2 and ErbB3 are active only in the context of ErbB heterodimers, and ErbB2-ErbB3 heterodimers, which are driven by Nrg (Neuregulin) ligands, are the most prevalent and potent complexes in terms of cell growth and transformation. The basis for the potency of signaling by the ligand-activated ErbB2-ErbB3 heterodimer lies in the fact that this dimer has the capacity to signal very potently, both through the Ras-ERK (Extracellular Signal Regulated Kinase) pathway for proliferation, and through the PI3K-Akt/PKB (Phosphatidylinositol-3 Kinase-Akt/Protein Kinase-B) pathway for survival. In addition, this receptor dimer evades downregulation mechanisms, leading to prolonged signaling.
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1.Lipid rafts and the local density of ErbB proteins influence the biological role of homo- and heteroassociations of ErbB2.
Nagy P, Vereb G, Sebestyen Z, Horvath G, Lockett SJ, Damjanovich S, Park JW, Jovin TM, Szollosi J. J Cell Sci. 2002 Nov 15;115(Pt 22):4251-62. 2.ErbB2 is required for muscle spindle and myoblast cell survival. Andrechek ER, Hardy WR, Girgis-Gabardo AA, Perry RL, Butler R, Graham FL, Kahn RC, Rudnicki MA, Muller WJ. Mol Cell Biol. 2002 Jul;22(13):4714-22. 3.The deaf and the dumb: the biology of ErbB-2 and ErbB-3. Citri A, Skaria KB, Yarden Y. Exp Cell Res. 2003 Mar 10;284(1):54-65.
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