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 journalArticle

51 Citations (Scopus)

Abstract

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
Volume296
Issue number1
DOIs
StatePublished - Sep 20 2002

Fingerprint

EphA2 Receptor
RING Finger Domains
Protein-Tyrosine Kinases
Eph Family Receptors
Proto-Oncogenes
Oncogene Proteins
Ligases
Ubiquitin
Point Mutation
Phosphotransferases
Amino Acids

Keywords

  • Cbl
  • Eph
  • Ephrin
  • Phosphorylation
  • Tyrosine kinase

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Wang, Y. J., Ota, S., Kataoka, H., Kanamori, M., Li, Z. Y., Band, H., ... Sugimura, H. (2002). Negative regulation of EphA2 receptor by Cbl. Biochemical and Biophysical Research Communications, 296(1), 214-220. https://doi.org/10.1016/S0006-291X(02)00806-9

Negative regulation of EphA2 receptor by Cbl. / Wang, You jie; Ota, Satoshi; Kataoka, Hideki; Kanamori, Masao; Li, Zhong you; Band, Hamid; Tanaka, Masamitsu; Sugimura, Haruhiko.

In: Biochemical and Biophysical Research Communications, Vol. 296, No. 1, 20.09.2002, p. 214-220.

Research output: Contribution to journalArticle

Wang, YJ, Ota, S, Kataoka, H, Kanamori, M, Li, ZY, Band, H, Tanaka, M & Sugimura, H 2002, 'Negative regulation of EphA2 receptor by Cbl', Biochemical and Biophysical Research Communications, vol. 296, no. 1, pp. 214-220. https://doi.org/10.1016/S0006-291X(02)00806-9
Wang, You jie ; Ota, Satoshi ; Kataoka, Hideki ; Kanamori, Masao ; Li, Zhong you ; Band, Hamid ; Tanaka, Masamitsu ; Sugimura, Haruhiko. / Negative regulation of EphA2 receptor by Cbl. In: Biochemical and Biophysical Research Communications. 2002 ; Vol. 296, No. 1. pp. 214-220.
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