Proteolytic Activation of Etk/Bmx Tyrosine Kinase by Caspases

Yi Mi Wu, Chia Lin Huang, Hsing Jien Kung, Chi Ying F Huang

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Etk/Bmx is a member of the Btk/Tec family of kinases, which are characterized by having a pleckstrin homology domain at the N terminus, in addition to the Src homology 3 (SH3), SH2, and the catalytic domains, shared with the Src family kinases. Etk, or Btk kinases in general, has been implicated in the regulation of apoptosis. To test whether Etk is the substrate for caspases during apoptosis, in vitro translated [ 35S]methionine-labeled Etk was incubated with different apoptotic extracts and recombinant caspases, respectively. Results showed that Etk was proteolyzed in all conditions tested with identical cleavage patterns. Caspase-mediated cleavage of Etk generated a C-terminal fragment, containing the complete SH2 and tyrosine kinase domains, but without intact pleckstrin homology and SH3 domains. This fragment has 4-fold higher kinase activity than that of the full-length Etk. Ectopic expression of the C-terminal fragment of Etk sensitized the PC3 prostate cancer cells to apoptosis in response to apoptosis-inducing stimuli. The finding, together with an earlier report that Etk is potentially antiapoptotic, suggests that Etk may serve as an apoptotic switch, depending on the forms of Etk existing inside the cells. To our knowledge, this is the first case where the activity of a tyrosine kinase is induced by caspase cleavage.

Original languageEnglish
Pages (from-to)17672-17678
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number21
DOIs
Publication statusPublished - Jan 25 2001
Externally publishedYes

Fingerprint

Caspases
Protein-Tyrosine Kinases
Chemical activation
Apoptosis
Phosphotransferases
src Homology Domains
src-Family Kinases
Methionine
Catalytic Domain
Prostatic Neoplasms
Cells
Switches
Substrates
platelet protein P47

ASJC Scopus subject areas

  • Biochemistry

Cite this

Proteolytic Activation of Etk/Bmx Tyrosine Kinase by Caspases. / Wu, Yi Mi; Huang, Chia Lin; Kung, Hsing Jien; Huang, Chi Ying F.

In: Journal of Biological Chemistry, Vol. 276, No. 21, 25.01.2001, p. 17672-17678.

Research output: Contribution to journalArticle

Wu, Yi Mi ; Huang, Chia Lin ; Kung, Hsing Jien ; Huang, Chi Ying F. / Proteolytic Activation of Etk/Bmx Tyrosine Kinase by Caspases. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 21. pp. 17672-17678.
@article{fceafa8a908f47a695948d9b541b3413,
title = "Proteolytic Activation of Etk/Bmx Tyrosine Kinase by Caspases",
abstract = "Etk/Bmx is a member of the Btk/Tec family of kinases, which are characterized by having a pleckstrin homology domain at the N terminus, in addition to the Src homology 3 (SH3), SH2, and the catalytic domains, shared with the Src family kinases. Etk, or Btk kinases in general, has been implicated in the regulation of apoptosis. To test whether Etk is the substrate for caspases during apoptosis, in vitro translated [ 35S]methionine-labeled Etk was incubated with different apoptotic extracts and recombinant caspases, respectively. Results showed that Etk was proteolyzed in all conditions tested with identical cleavage patterns. Caspase-mediated cleavage of Etk generated a C-terminal fragment, containing the complete SH2 and tyrosine kinase domains, but without intact pleckstrin homology and SH3 domains. This fragment has 4-fold higher kinase activity than that of the full-length Etk. Ectopic expression of the C-terminal fragment of Etk sensitized the PC3 prostate cancer cells to apoptosis in response to apoptosis-inducing stimuli. The finding, together with an earlier report that Etk is potentially antiapoptotic, suggests that Etk may serve as an apoptotic switch, depending on the forms of Etk existing inside the cells. To our knowledge, this is the first case where the activity of a tyrosine kinase is induced by caspase cleavage.",
author = "Wu, {Yi Mi} and Huang, {Chia Lin} and Kung, {Hsing Jien} and Huang, {Chi Ying F}",
year = "2001",
month = "1",
day = "25",
doi = "10.1074/jbc.M010964200",
language = "English",
volume = "276",
pages = "17672--17678",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "21",

}

TY - JOUR

T1 - Proteolytic Activation of Etk/Bmx Tyrosine Kinase by Caspases

AU - Wu, Yi Mi

AU - Huang, Chia Lin

AU - Kung, Hsing Jien

AU - Huang, Chi Ying F

PY - 2001/1/25

Y1 - 2001/1/25

N2 - Etk/Bmx is a member of the Btk/Tec family of kinases, which are characterized by having a pleckstrin homology domain at the N terminus, in addition to the Src homology 3 (SH3), SH2, and the catalytic domains, shared with the Src family kinases. Etk, or Btk kinases in general, has been implicated in the regulation of apoptosis. To test whether Etk is the substrate for caspases during apoptosis, in vitro translated [ 35S]methionine-labeled Etk was incubated with different apoptotic extracts and recombinant caspases, respectively. Results showed that Etk was proteolyzed in all conditions tested with identical cleavage patterns. Caspase-mediated cleavage of Etk generated a C-terminal fragment, containing the complete SH2 and tyrosine kinase domains, but without intact pleckstrin homology and SH3 domains. This fragment has 4-fold higher kinase activity than that of the full-length Etk. Ectopic expression of the C-terminal fragment of Etk sensitized the PC3 prostate cancer cells to apoptosis in response to apoptosis-inducing stimuli. The finding, together with an earlier report that Etk is potentially antiapoptotic, suggests that Etk may serve as an apoptotic switch, depending on the forms of Etk existing inside the cells. To our knowledge, this is the first case where the activity of a tyrosine kinase is induced by caspase cleavage.

AB - Etk/Bmx is a member of the Btk/Tec family of kinases, which are characterized by having a pleckstrin homology domain at the N terminus, in addition to the Src homology 3 (SH3), SH2, and the catalytic domains, shared with the Src family kinases. Etk, or Btk kinases in general, has been implicated in the regulation of apoptosis. To test whether Etk is the substrate for caspases during apoptosis, in vitro translated [ 35S]methionine-labeled Etk was incubated with different apoptotic extracts and recombinant caspases, respectively. Results showed that Etk was proteolyzed in all conditions tested with identical cleavage patterns. Caspase-mediated cleavage of Etk generated a C-terminal fragment, containing the complete SH2 and tyrosine kinase domains, but without intact pleckstrin homology and SH3 domains. This fragment has 4-fold higher kinase activity than that of the full-length Etk. Ectopic expression of the C-terminal fragment of Etk sensitized the PC3 prostate cancer cells to apoptosis in response to apoptosis-inducing stimuli. The finding, together with an earlier report that Etk is potentially antiapoptotic, suggests that Etk may serve as an apoptotic switch, depending on the forms of Etk existing inside the cells. To our knowledge, this is the first case where the activity of a tyrosine kinase is induced by caspase cleavage.

UR - http://www.scopus.com/inward/record.url?scp=0035947704&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035947704&partnerID=8YFLogxK

U2 - 10.1074/jbc.M010964200

DO - 10.1074/jbc.M010964200

M3 - Article

VL - 276

SP - 17672

EP - 17678

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 21

ER -