Receptor protein tyrosine kinases (PTKs) have been classified into different subclasses on the basis of sequence similarity and distinct structural characteristics. The c-Met encoded receptor represents the initial member of one class of receptors characterized by a heterodimeric structure and a cysteine-rich extracellular domain. Ron, also designated macrophage-stimulating protein receptor (MSP receptor), p185-Ron, CD136 antigen or PTK8 represents a second member of this receptor class. The intracellular PTK domains of Ron and Met are highly similar (63% sequence identity) while the extracellular domains are less related (25% sequence identity) and both are rich in cysteine residues. Mature Ron receptor is comprised of a disulfide-linked heterodimer formed from an alpha chain (Ron α) and a beta chain (Ron β). Proteolytic processing results in the separation of the N-terminal Ron α and C-terminal Ron β subunits.
