Autoinhibition of the Ron receptor tyrosine kinase by the juxtamembrane domain

Xin Wang, Neela Yennawar, Pamela A. Hankey

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Background: The Ron receptor tyrosine kinase (RTK) has been implicated in the progression of a number of carcinomas, thus understanding the regulatory mechanisms governing its activity is of potential therapeutic significance. A critical role for the juxtamembrane domain in regulating RTK activity is emerging, however the mechanism by which this regulation occurs varies considerably from receptor to receptor. Results: Unlike other RTKs described to date, tyrosines in the juxtamembrane domain of Ron are inconsequential for receptor activation. Rather, we have identified an acidic region in the juxtamembrane domain of Ron that plays a central role in promoting receptor autoinhibition. Furthermore, our studies demonstrate that phosphorylation of Y1198 in the kinase domain promotes Ron activation, likely by relieving the inhibitory constraints imposed by the juxtamembrane domain. Conclusions: Taken together, our experimental data and molecular modeling provide a better understanding of the mechanisms governing Ron activation, which will lay the groundwork for the development of novel therapeutic approaches for targeting Ron in human malignancies.

Original languageEnglish (US)
Article number28
JournalCell Communication and Signaling
Issue number1
StatePublished - Apr 16 2014

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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