title: Autoinhibition of the Ron receptor tyrosine kinase by the juxtamembrane domain.
abstract: 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.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Neela
authors.initials: N
authors.lastname: Yennawar
authors.affiliation: Graduate Program in Cell and Developmental Biology, The Pennsylvania State University, University Park, PA 16802, USA. phc7@psu.edu.
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Hankey
mesh_terms: D000595:Amino Acid Sequence; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry* / Q000378:metabolism
chemical_list: C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases
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