The ErbB signaling network in embryogenesis and oncogenesis: signal diversification through combinatorial ligand‐receptor interactions

Ligand‐induced activation of receptor tyrosine kinases (RTK) results in the initiation of diverse cellular pathways, including proliferation, differentiation and cell migration. The ErbB family of RTKs represents a model for signal diversification through the formation of homo‐ and heterodimeric receptor complexes. Each dimeric receptor complex will initiate a distinct signaling pathway by recruiting a different set of Src homology 2‐ (SH2‐) containing effector proteins. Further complexity is added due to the existence of an oncogenic receptor that enhances and stabilizes dimerization but has no ligand (ErbB‐2), and a receptor that can recruit novel SH‐2‐containing proteins, but is itself devoid of kinase activity (ErbB‐3). The resulting signaling network has important implications for embryonic development and malignant transformation.

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