The Crystal Structure of a Constitutively Active Mutant RON Kinase Suggests an Intramolecular Autophosphorylation Hypothesis

A complex of RONM1254T with AMP-PNP and Mg2+ reveals a substratelike positioning of Tyr1238 as well as likely catalysis-competent placement of the AMP-PNP and Mg2+ components and indicates a tendency for cis phosphorylation. The structure shows how the oncogenic mutation may cause the constitutive activation and suggests a mechanistic hypothesis for the autophosphorylation of receptor tyrosine kinases.