CD28 is associated with and induces the immediate tyrosine phosphorylation and activation of the Tec family kinase ITK/EMT in the human Jurkat leukemic T-cell line

Avery August, Spencer Gibson, Yuko Kawakami, Toshiaki Kawakami, Gordon Mills, Bo Dupont

Research output: Contribution to journalArticle

204 Citations (Scopus)

Abstract

T lymphocytes require two signals to be activated. The antigen-specific T- cell receptor can deliver the first signal, while ligation of the T-cell surface molecule CD28 by antibodies or its cognate ligands B7-1 (CD80) or B7- 2 has been demonstrated to be sufficient for the delivery of the second signal. Signaling via CD28 and the T-cell receptor results (i) in their costimulation of T cells to produce numerous lymphokines including interleukin 2 and (ii) in the prevention of anergy induction. Little is known about the pathway by which CD28 mediates its signals except that protein- tyrosine phosphorylation is involved. We show here in human Jurkat cells that the Tec-family protein-tyrosine kinase ITK/EMT (p72(ITK/EMT)) is associated with CD28 and becomes tyrosine-phosphorylated and activated within seconds of CD28 ligation. This tyrosine phosphorylation of p72(ITK/EMT) is rapid (within 30 sec), occurs in the absence of LCK activation, and precedes tyrosine phosphorylation of the guanine nucleotide exchange factor VAV. Secondary crosslinking of CD28 is unnecessary for the induced tyrosine phosphorylation of p72(ITK/EMT). Thus, tyrosine phosphorylation of p72(ITK/EMT) may represent one of the earliest events in CD28 signaling. This demonstrates that a member of the Tec family of protein tyrosine kinases, similar to members of the Src and Syk families, plays a role in the activation of T cells. Furthermore, the data demonstrate that p72(ITK/EMT), and by analogy other members of the Tec family, responds to extracellularly generated signals.

Original languageEnglish (US)
Pages (from-to)9347-9351
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number20
DOIs
StatePublished - Sep 27 1994
Externally publishedYes

Fingerprint

Tyrosine
Phosphorylation
T-Lymphocytes
Cell Line
T-Cell Antigen Receptor
Ligation
CD80 Antigens
Guanine Nucleotide Exchange Factors
Jurkat Cells
Lymphokines
Interleukin-2
Tec protein-tyrosine kinase
Antibodies
Proteins

Keywords

  • costimulation
  • lymphocyte activation
  • signal transduction
  • tyrosine kinase
  • vav

ASJC Scopus subject areas

  • General

Cite this

CD28 is associated with and induces the immediate tyrosine phosphorylation and activation of the Tec family kinase ITK/EMT in the human Jurkat leukemic T-cell line. / August, Avery; Gibson, Spencer; Kawakami, Yuko; Kawakami, Toshiaki; Mills, Gordon; Dupont, Bo.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 20, 27.09.1994, p. 9347-9351.

Research output: Contribution to journalArticle

@article{89a748fd430d4a63ab3ae4197cfe41ab,
title = "CD28 is associated with and induces the immediate tyrosine phosphorylation and activation of the Tec family kinase ITK/EMT in the human Jurkat leukemic T-cell line",
abstract = "T lymphocytes require two signals to be activated. The antigen-specific T- cell receptor can deliver the first signal, while ligation of the T-cell surface molecule CD28 by antibodies or its cognate ligands B7-1 (CD80) or B7- 2 has been demonstrated to be sufficient for the delivery of the second signal. Signaling via CD28 and the T-cell receptor results (i) in their costimulation of T cells to produce numerous lymphokines including interleukin 2 and (ii) in the prevention of anergy induction. Little is known about the pathway by which CD28 mediates its signals except that protein- tyrosine phosphorylation is involved. We show here in human Jurkat cells that the Tec-family protein-tyrosine kinase ITK/EMT (p72(ITK/EMT)) is associated with CD28 and becomes tyrosine-phosphorylated and activated within seconds of CD28 ligation. This tyrosine phosphorylation of p72(ITK/EMT) is rapid (within 30 sec), occurs in the absence of LCK activation, and precedes tyrosine phosphorylation of the guanine nucleotide exchange factor VAV. Secondary crosslinking of CD28 is unnecessary for the induced tyrosine phosphorylation of p72(ITK/EMT). Thus, tyrosine phosphorylation of p72(ITK/EMT) may represent one of the earliest events in CD28 signaling. This demonstrates that a member of the Tec family of protein tyrosine kinases, similar to members of the Src and Syk families, plays a role in the activation of T cells. Furthermore, the data demonstrate that p72(ITK/EMT), and by analogy other members of the Tec family, responds to extracellularly generated signals.",
keywords = "costimulation, lymphocyte activation, signal transduction, tyrosine kinase, vav",
author = "Avery August and Spencer Gibson and Yuko Kawakami and Toshiaki Kawakami and Gordon Mills and Bo Dupont",
year = "1994",
month = "9",
day = "27",
doi = "10.1073/pnas.91.20.9347",
language = "English (US)",
volume = "91",
pages = "9347--9351",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "20",

}

TY - JOUR

T1 - CD28 is associated with and induces the immediate tyrosine phosphorylation and activation of the Tec family kinase ITK/EMT in the human Jurkat leukemic T-cell line

AU - August, Avery

AU - Gibson, Spencer

AU - Kawakami, Yuko

AU - Kawakami, Toshiaki

AU - Mills, Gordon

AU - Dupont, Bo

PY - 1994/9/27

Y1 - 1994/9/27

N2 - T lymphocytes require two signals to be activated. The antigen-specific T- cell receptor can deliver the first signal, while ligation of the T-cell surface molecule CD28 by antibodies or its cognate ligands B7-1 (CD80) or B7- 2 has been demonstrated to be sufficient for the delivery of the second signal. Signaling via CD28 and the T-cell receptor results (i) in their costimulation of T cells to produce numerous lymphokines including interleukin 2 and (ii) in the prevention of anergy induction. Little is known about the pathway by which CD28 mediates its signals except that protein- tyrosine phosphorylation is involved. We show here in human Jurkat cells that the Tec-family protein-tyrosine kinase ITK/EMT (p72(ITK/EMT)) is associated with CD28 and becomes tyrosine-phosphorylated and activated within seconds of CD28 ligation. This tyrosine phosphorylation of p72(ITK/EMT) is rapid (within 30 sec), occurs in the absence of LCK activation, and precedes tyrosine phosphorylation of the guanine nucleotide exchange factor VAV. Secondary crosslinking of CD28 is unnecessary for the induced tyrosine phosphorylation of p72(ITK/EMT). Thus, tyrosine phosphorylation of p72(ITK/EMT) may represent one of the earliest events in CD28 signaling. This demonstrates that a member of the Tec family of protein tyrosine kinases, similar to members of the Src and Syk families, plays a role in the activation of T cells. Furthermore, the data demonstrate that p72(ITK/EMT), and by analogy other members of the Tec family, responds to extracellularly generated signals.

AB - T lymphocytes require two signals to be activated. The antigen-specific T- cell receptor can deliver the first signal, while ligation of the T-cell surface molecule CD28 by antibodies or its cognate ligands B7-1 (CD80) or B7- 2 has been demonstrated to be sufficient for the delivery of the second signal. Signaling via CD28 and the T-cell receptor results (i) in their costimulation of T cells to produce numerous lymphokines including interleukin 2 and (ii) in the prevention of anergy induction. Little is known about the pathway by which CD28 mediates its signals except that protein- tyrosine phosphorylation is involved. We show here in human Jurkat cells that the Tec-family protein-tyrosine kinase ITK/EMT (p72(ITK/EMT)) is associated with CD28 and becomes tyrosine-phosphorylated and activated within seconds of CD28 ligation. This tyrosine phosphorylation of p72(ITK/EMT) is rapid (within 30 sec), occurs in the absence of LCK activation, and precedes tyrosine phosphorylation of the guanine nucleotide exchange factor VAV. Secondary crosslinking of CD28 is unnecessary for the induced tyrosine phosphorylation of p72(ITK/EMT). Thus, tyrosine phosphorylation of p72(ITK/EMT) may represent one of the earliest events in CD28 signaling. This demonstrates that a member of the Tec family of protein tyrosine kinases, similar to members of the Src and Syk families, plays a role in the activation of T cells. Furthermore, the data demonstrate that p72(ITK/EMT), and by analogy other members of the Tec family, responds to extracellularly generated signals.

KW - costimulation

KW - lymphocyte activation

KW - signal transduction

KW - tyrosine kinase

KW - vav

UR - http://www.scopus.com/inward/record.url?scp=0028146530&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028146530&partnerID=8YFLogxK

U2 - 10.1073/pnas.91.20.9347

DO - 10.1073/pnas.91.20.9347

M3 - Article

C2 - 7524075

AN - SCOPUS:0028146530

VL - 91

SP - 9347

EP - 9351

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 - 20

ER -