The C terminus of RON tyrosine kinase plays an autoinhibitory role.

Article Details


Yokoyama N, Ischenko I, Hayman MJ, Miller WT

The C terminus of RON tyrosine kinase plays an autoinhibitory role.

J Biol Chem. 2005 Mar 11;280(10):8893-900. doi: 10.1074/jbc.M412623200. Epub 2005 Jan 4.

PubMed ID
15632155 [ View in PubMed

RON is a receptor tyrosine kinase in the MET family. We have expressed and purified active RON using the Sf9/baculovirus system. The constructs used in this study comprise the kinase domain alone and the kinase domain plus the C-terminal region. The construct containing the kinase domain alone has a higher specific activity than the construct containing the kinase and C-terminal domains. Purified RON undergoes autophosphorylation, and the exogenous RON C terminus serves as a substrate. Peptides containing a dityrosine motif derived from the C-terminal tail inhibit RON in vitro or when delivered into intact cells, consistent with an autoinhibitory mechanism. Phenylalanine substitutions within these peptides increase the inhibitory potency. Moreover, introduction of these Phe residues into the dityrosine motif of the RON kinase leads to a decrease in kinase activity. Taken together, our data suggest a model in which the C-terminal tail of RON regulates kinase activity via an interaction with the kinase catalytic domain.

DrugBank Data that Cites this Article

NameUniProt ID
Macrophage-stimulating protein receptorQ04912Details