Negative regulation of EphA2 receptor by Cbl

You jie Wang, Satoshi Ota, Hideki Kataoka, Masao Kanamori, Zhong you Li, Hamid Band, Masamitsu Tanaka, Haruhiko Sugimura

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


The c-Cbl proto-oncogene product Cbl has emerged as a negative regulator of receptor and non-receptor tyrosine kinases, a function dependent on its recently identified ubiquitin ligase activity. Here, we report that EphA2, a member of Eph receptor tyrosine kinases is negatively regulated by Cbl. The negative regulation of EphA2 mediated by Cbl is dependent on the activity of EphA2, as the kinase inactive mutant of EphA2 cannot be regulated by Cbl. Moreover, a point mutation (G306E-Cbl) in TKB region of Cbl that has been reported to abolish Cbl binding to RTKs and non-receptor tyrosine kinases impaired the binding to active EphA2. The dominant negative mutant 70Z-Cbl, which has a 17-amino acids deletion in the N-boundary of the RING finger domain, defuncted negative regulatory function of Cbl to EphA2. These results demonstrate that the TKB domain and RING finger domain of Cbl are essential for this negative regulation.

Original languageEnglish (US)
Pages (from-to)214-220
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number1
StatePublished - 2002
Externally publishedYes


  • Cbl
  • Eph
  • Ephrin
  • Phosphorylation
  • Tyrosine kinase

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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