Evidence of both extra- and intracellular cysteine targets of protein modification for activation of RET kinase

Anwarul A. Akhand, Takanari Ikeyama, Satoru Akazawa, Masashi Kato, Khaled Hossain, Kozue Takeda, Haruhiko Suzuki, Masahide Takahashi, Izumi Nakashima

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

By use of a specifically sulfhydryl group-reactive chemical, 1,4-butanediyl-bismethanethiosulfonate (BMTS), we studied the localization of oxidative stress-responsive target cysteines for activation of a receptor-type protein tyrosine kinase, c-RET. The chemical, which reacted with RET proteins on the cell surface for sulfhydryl-linked aggregation, induced autophosphorylation and activation of RET kinase. When extracellular domain-deleted RET mutant (RET-PTC-1) cells were exposed to BMTS, neither the molecular status nor the activity of the enzyme was affected, suggesting that the target cysteines of BMTS to which cells were exposed for reaction are located in the cysteine-rich region of the extracellular domain of RET kinase. Despite this result, the exposure of a subcellular form of c-RET or RET-PTC-1 kinase isolated by immunoprecipitation to BMTS did induce activation of the enzyme. These results suggest that cysteines in both the extracellular and the intracellular domains of RET can work as target sites of accessible BMTS and possibly other oxidative elements for structural modification and activation of RET kinase.

Original languageEnglish
Pages (from-to)826-831
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume292
Issue number4
DOIs
Publication statusPublished - 12-04-2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Evidence of both extra- and intracellular cysteine targets of protein modification for activation of RET kinase'. Together they form a unique fingerprint.

Cite this