T-cell receptor complex is essential for Fas signal transduction

Askar M. Akimzhanov, Xinmin Wang, Jiaren Sun, Darren Boehning

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The Fas receptor (also known as CD95 and APO-1) is a member of the tumor necrosis factor α-family of death receptors that mediate T-cell responses. Here, we show that Fas receptor signaling requires a functional T-cell receptor (TCR) complex. Fas receptor directly binds to and activates TCR components in a stimulus-dependent manner. Fas receptor stimulation does not activate canonical downstream TCR pathways, but instead the TCR complex is required specifically for Fas-mediated calcium release. Importantly, null mutations in Lck, ZAP70, and the TCR α- and β-chains abrogate Fas signaling. Our results reveal a direct role for the TCR complex in mediating Fas-specific signaling events critical for T-cell homeostasis.

Original languageEnglish (US)
Pages (from-to)15105-15110
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number34
DOIs
StatePublished - Aug 24 2010

Fingerprint

T-Cell Antigen Receptor
CD95 Antigens
Signal Transduction
T-Lymphocytes
Death Domain Receptors
Cellular Structures
Homeostasis
Tumor Necrosis Factor-alpha
Calcium
Mutation

Keywords

  • Apoptosis
  • Calcium
  • Lck

ASJC Scopus subject areas

  • General

Cite this

T-cell receptor complex is essential for Fas signal transduction. / Akimzhanov, Askar M.; Wang, Xinmin; Sun, Jiaren; Boehning, Darren.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 34, 24.08.2010, p. 15105-15110.

Research output: Contribution to journalArticle

Akimzhanov, Askar M. ; Wang, Xinmin ; Sun, Jiaren ; Boehning, Darren. / T-cell receptor complex is essential for Fas signal transduction. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 34. pp. 15105-15110.
@article{985a5ceb9777471cbf722cc5fe199bc4,
title = "T-cell receptor complex is essential for Fas signal transduction",
abstract = "The Fas receptor (also known as CD95 and APO-1) is a member of the tumor necrosis factor α-family of death receptors that mediate T-cell responses. Here, we show that Fas receptor signaling requires a functional T-cell receptor (TCR) complex. Fas receptor directly binds to and activates TCR components in a stimulus-dependent manner. Fas receptor stimulation does not activate canonical downstream TCR pathways, but instead the TCR complex is required specifically for Fas-mediated calcium release. Importantly, null mutations in Lck, ZAP70, and the TCR α- and β-chains abrogate Fas signaling. Our results reveal a direct role for the TCR complex in mediating Fas-specific signaling events critical for T-cell homeostasis.",
keywords = "Apoptosis, Calcium, Lck",
author = "Akimzhanov, {Askar M.} and Xinmin Wang and Jiaren Sun and Darren Boehning",
year = "2010",
month = "8",
day = "24",
doi = "10.1073/pnas.1005419107",
language = "English (US)",
volume = "107",
pages = "15105--15110",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "34",

}

TY - JOUR

T1 - T-cell receptor complex is essential for Fas signal transduction

AU - Akimzhanov, Askar M.

AU - Wang, Xinmin

AU - Sun, Jiaren

AU - Boehning, Darren

PY - 2010/8/24

Y1 - 2010/8/24

N2 - The Fas receptor (also known as CD95 and APO-1) is a member of the tumor necrosis factor α-family of death receptors that mediate T-cell responses. Here, we show that Fas receptor signaling requires a functional T-cell receptor (TCR) complex. Fas receptor directly binds to and activates TCR components in a stimulus-dependent manner. Fas receptor stimulation does not activate canonical downstream TCR pathways, but instead the TCR complex is required specifically for Fas-mediated calcium release. Importantly, null mutations in Lck, ZAP70, and the TCR α- and β-chains abrogate Fas signaling. Our results reveal a direct role for the TCR complex in mediating Fas-specific signaling events critical for T-cell homeostasis.

AB - The Fas receptor (also known as CD95 and APO-1) is a member of the tumor necrosis factor α-family of death receptors that mediate T-cell responses. Here, we show that Fas receptor signaling requires a functional T-cell receptor (TCR) complex. Fas receptor directly binds to and activates TCR components in a stimulus-dependent manner. Fas receptor stimulation does not activate canonical downstream TCR pathways, but instead the TCR complex is required specifically for Fas-mediated calcium release. Importantly, null mutations in Lck, ZAP70, and the TCR α- and β-chains abrogate Fas signaling. Our results reveal a direct role for the TCR complex in mediating Fas-specific signaling events critical for T-cell homeostasis.

KW - Apoptosis

KW - Calcium

KW - Lck

UR - http://www.scopus.com/inward/record.url?scp=77956992336&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77956992336&partnerID=8YFLogxK

U2 - 10.1073/pnas.1005419107

DO - 10.1073/pnas.1005419107

M3 - Article

C2 - 20696918

AN - SCOPUS:77956992336

VL - 107

SP - 15105

EP - 15110

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 34

ER -