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Ligand Binding

A large and compelling body of data indicate that ligand binding causes dimerization of two RTK polypeptides, or in the case of the preassembled IR (βααβ) structure, ligand promotes an even more intimate coupling between the two αβ half-receptors.[15-19]Importantly, this ligand-induced dimerization is indispensable to the ability of ligand to activate the kinase catalytic function. Mutations in the RTK or ligand that inhibit dimerization prevent ligand-dependent kinase activation and a variety of mutations or gene translocations that cause ligand-independent dimerization of the kinase domain are sufficient to cause ligand-independent kinase activation. As regards the mechanisms underlying dimerization, several are now directly established. Growth hormone provided the first example of a monomeric ligand that has two binding surfaces and dimerizes two receptor polypeptides. In the ErbB/EGFR family, although the ligand has two separate contact surfaces for the receptor, both …