Src-like adaptor protein (SLAP) is a negative regulator of T cell receptor signaling

Tomasz Sosinowski, Akhilesh Pandey, Vishva M. Dixit, Arthur Weiss

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Initiation of T cell antigen receptor (TCR) signaling is dependent on Lck, a Src family kinase. The Src-like adaptor protein (SLAP) contains Src homology (SH)3 and SH2 domains, which are highly homologous to those of Lck and other Src family members. Because of the structural similarity between Lck and SLAP, we studied its potential role in TCR signaling. Here, we show that SLAP is expressed in T cells, and that when expressed in Jurkat T cells it can specifically inhibit TCR signaling leading to nuclear factor of activated T cells (NFAT)-, activator protein 1 (AP-1)-, and interleukin 2-dependent transcription. The SH3 and SH2 domains of SLAP are required for maximal attenuation of TCR signaling. This inhibitory activity can be bypassed by the combination of phorbol myristate acetate (PMA) and ionomycin, suggesting that SLAP acts proximally in the TCR signaling pathway. SLAP colocalizes with endosomes in Jurkat and in HeLa cells, and is insoluble in mild detergents. In stimulated Jurkat cells, SLAP associates with a molecular signaling complex containing CD3ζ, ZAP-70, SH2 domain-containing leukocyte protein of 76 kD (SLP-76), Vav, and possibly linker for activation of T cells (LAT). These results suggest that SLAP is a negative regulator of TCR signaling.

Original languageEnglish (US)
Pages (from-to)463-473
Number of pages11
JournalJournal of Experimental Medicine
Volume191
Issue number3
DOIs
StatePublished - Feb 7 2000
Externally publishedYes

Fingerprint

T-Cell Antigen Receptor
src Homology Domains
Proteins
Jurkat Cells
T-Lymphocytes
CD3 Antigens
NFATC Transcription Factors
Ionomycin
src-Family Kinases
Endosomes
Transcription Factor AP-1
Tetradecanoylphorbol Acetate
HeLa Cells
Detergents
Interleukin-2
Leukocytes

Keywords

  • Calcium flux
  • Endosomes
  • Lck
  • Src homology 2
  • T cell activation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Src-like adaptor protein (SLAP) is a negative regulator of T cell receptor signaling. / Sosinowski, Tomasz; Pandey, Akhilesh; Dixit, Vishva M.; Weiss, Arthur.

In: Journal of Experimental Medicine, Vol. 191, No. 3, 07.02.2000, p. 463-473.

Research output: Contribution to journalArticle

Sosinowski, Tomasz ; Pandey, Akhilesh ; Dixit, Vishva M. ; Weiss, Arthur. / Src-like adaptor protein (SLAP) is a negative regulator of T cell receptor signaling. In: Journal of Experimental Medicine. 2000 ; Vol. 191, No. 3. pp. 463-473.
@article{648a89e322fb46649a5f4dc7ca5a5ea2,
title = "Src-like adaptor protein (SLAP) is a negative regulator of T cell receptor signaling",
abstract = "Initiation of T cell antigen receptor (TCR) signaling is dependent on Lck, a Src family kinase. The Src-like adaptor protein (SLAP) contains Src homology (SH)3 and SH2 domains, which are highly homologous to those of Lck and other Src family members. Because of the structural similarity between Lck and SLAP, we studied its potential role in TCR signaling. Here, we show that SLAP is expressed in T cells, and that when expressed in Jurkat T cells it can specifically inhibit TCR signaling leading to nuclear factor of activated T cells (NFAT)-, activator protein 1 (AP-1)-, and interleukin 2-dependent transcription. The SH3 and SH2 domains of SLAP are required for maximal attenuation of TCR signaling. This inhibitory activity can be bypassed by the combination of phorbol myristate acetate (PMA) and ionomycin, suggesting that SLAP acts proximally in the TCR signaling pathway. SLAP colocalizes with endosomes in Jurkat and in HeLa cells, and is insoluble in mild detergents. In stimulated Jurkat cells, SLAP associates with a molecular signaling complex containing CD3ζ, ZAP-70, SH2 domain-containing leukocyte protein of 76 kD (SLP-76), Vav, and possibly linker for activation of T cells (LAT). These results suggest that SLAP is a negative regulator of TCR signaling.",
keywords = "Calcium flux, Endosomes, Lck, Src homology 2, T cell activation",
author = "Tomasz Sosinowski and Akhilesh Pandey and Dixit, {Vishva M.} and Arthur Weiss",
year = "2000",
month = "2",
day = "7",
doi = "10.1084/jem.191.3.463",
language = "English (US)",
volume = "191",
pages = "463--473",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "3",

}

TY - JOUR

T1 - Src-like adaptor protein (SLAP) is a negative regulator of T cell receptor signaling

AU - Sosinowski, Tomasz

AU - Pandey, Akhilesh

AU - Dixit, Vishva M.

AU - Weiss, Arthur

PY - 2000/2/7

Y1 - 2000/2/7

N2 - Initiation of T cell antigen receptor (TCR) signaling is dependent on Lck, a Src family kinase. The Src-like adaptor protein (SLAP) contains Src homology (SH)3 and SH2 domains, which are highly homologous to those of Lck and other Src family members. Because of the structural similarity between Lck and SLAP, we studied its potential role in TCR signaling. Here, we show that SLAP is expressed in T cells, and that when expressed in Jurkat T cells it can specifically inhibit TCR signaling leading to nuclear factor of activated T cells (NFAT)-, activator protein 1 (AP-1)-, and interleukin 2-dependent transcription. The SH3 and SH2 domains of SLAP are required for maximal attenuation of TCR signaling. This inhibitory activity can be bypassed by the combination of phorbol myristate acetate (PMA) and ionomycin, suggesting that SLAP acts proximally in the TCR signaling pathway. SLAP colocalizes with endosomes in Jurkat and in HeLa cells, and is insoluble in mild detergents. In stimulated Jurkat cells, SLAP associates with a molecular signaling complex containing CD3ζ, ZAP-70, SH2 domain-containing leukocyte protein of 76 kD (SLP-76), Vav, and possibly linker for activation of T cells (LAT). These results suggest that SLAP is a negative regulator of TCR signaling.

AB - Initiation of T cell antigen receptor (TCR) signaling is dependent on Lck, a Src family kinase. The Src-like adaptor protein (SLAP) contains Src homology (SH)3 and SH2 domains, which are highly homologous to those of Lck and other Src family members. Because of the structural similarity between Lck and SLAP, we studied its potential role in TCR signaling. Here, we show that SLAP is expressed in T cells, and that when expressed in Jurkat T cells it can specifically inhibit TCR signaling leading to nuclear factor of activated T cells (NFAT)-, activator protein 1 (AP-1)-, and interleukin 2-dependent transcription. The SH3 and SH2 domains of SLAP are required for maximal attenuation of TCR signaling. This inhibitory activity can be bypassed by the combination of phorbol myristate acetate (PMA) and ionomycin, suggesting that SLAP acts proximally in the TCR signaling pathway. SLAP colocalizes with endosomes in Jurkat and in HeLa cells, and is insoluble in mild detergents. In stimulated Jurkat cells, SLAP associates with a molecular signaling complex containing CD3ζ, ZAP-70, SH2 domain-containing leukocyte protein of 76 kD (SLP-76), Vav, and possibly linker for activation of T cells (LAT). These results suggest that SLAP is a negative regulator of TCR signaling.

KW - Calcium flux

KW - Endosomes

KW - Lck

KW - Src homology 2

KW - T cell activation

UR - http://www.scopus.com/inward/record.url?scp=0034614887&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034614887&partnerID=8YFLogxK

U2 - 10.1084/jem.191.3.463

DO - 10.1084/jem.191.3.463

M3 - Article

C2 - 10662792

AN - SCOPUS:0034614887

VL - 191

SP - 463

EP - 473

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 3

ER -