The EMT/ITK/TSK (EMT) tyrosine kinase is activated during TCR signaling

LCK is required for optimal activation of EMT

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

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Functional T lymphocyte activation requires concurrent stimulation of the TCR complex and an accessory molecule, most frequently CD28. We have previously demonstrated that the TEC family tyrosine kinase EMT/ITK/TSK (EMT) is activated following cross-linking of CD28. We demonstrate herein that cross-linking of the CD3 component of the TCR complex also leads to EMT activation as indicated by a rapid and transient increase in EMT tyrosine phosphorylation and kinase activity in anti-EMT immunoprecipitates. However, although concurrent cross-linking of the TCR and CD28 results in a marked increase in production of the T cell growth factor IL-2, it does not result in a significant alteration in the magnitude or duration of EMT activation. Somatic cell mutants of the Jurkat T cell line, which lack the SRC family kinase LCK (JCaM1.6), fail to produce IL-2 when stimulated through the TCR complex. EMT activation, as evidenced by increased EMT tyrosine phosphorylation and EMT-associated kinase activity, was also greatly reduced following stimulation of the TCR in the JCaM1.6 Jurkat T cell mutants that lack LCK. In support of a role for LCK in EMT activation, reconstitution of the LCK-negative Jurkat T cell line by enforced expression of LCK restored TCR-mediated EMT activation. Taken together, the data indicate that the EMT tyrosine kinase is activated following cross-linking of the TCR, a process in which LCK likely plays an important role.

Original languageEnglish (US)
Pages (from-to)2716-2722
Number of pages7
JournalJournal of Immunology
Volume156
Issue number8
StatePublished - Apr 15 1996

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Protein-Tyrosine Kinases
Jurkat Cells
Interleukin-2
T-Lymphocytes
Phosphotransferases
T-Cell Antigen Receptor-CD3 Complex
Phosphorylation
Cell Line
Lymphocyte Activation
Tyrosine

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Gibson, S., August, A., Kawakami, Y., Kawakami, T., Dupont, B., & Mills, G. B. (1996). The EMT/ITK/TSK (EMT) tyrosine kinase is activated during TCR signaling: LCK is required for optimal activation of EMT. Journal of Immunology, 156(8), 2716-2722.
Gibson, Spencer ; August, Avery ; Kawakami, Yuko ; Kawakami, Toshiaki ; Dupont, Bo ; Mills, Gordon B. / The EMT/ITK/TSK (EMT) tyrosine kinase is activated during TCR signaling : LCK is required for optimal activation of EMT. In: Journal of Immunology. 1996 ; Vol. 156, No. 8. pp. 2716-2722.
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abstract = "Functional T lymphocyte activation requires concurrent stimulation of the TCR complex and an accessory molecule, most frequently CD28. We have previously demonstrated that the TEC family tyrosine kinase EMT/ITK/TSK (EMT) is activated following cross-linking of CD28. We demonstrate herein that cross-linking of the CD3 component of the TCR complex also leads to EMT activation as indicated by a rapid and transient increase in EMT tyrosine phosphorylation and kinase activity in anti-EMT immunoprecipitates. However, although concurrent cross-linking of the TCR and CD28 results in a marked increase in production of the T cell growth factor IL-2, it does not result in a significant alteration in the magnitude or duration of EMT activation. Somatic cell mutants of the Jurkat T cell line, which lack the SRC family kinase LCK (JCaM1.6), fail to produce IL-2 when stimulated through the TCR complex. EMT activation, as evidenced by increased EMT tyrosine phosphorylation and EMT-associated kinase activity, was also greatly reduced following stimulation of the TCR in the JCaM1.6 Jurkat T cell mutants that lack LCK. In support of a role for LCK in EMT activation, reconstitution of the LCK-negative Jurkat T cell line by enforced expression of LCK restored TCR-mediated EMT activation. Taken together, the data indicate that the EMT tyrosine kinase is activated following cross-linking of the TCR, a process in which LCK likely plays an important role.",
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Gibson, S, August, A, Kawakami, Y, Kawakami, T, Dupont, B & Mills, GB 1996, 'The EMT/ITK/TSK (EMT) tyrosine kinase is activated during TCR signaling: LCK is required for optimal activation of EMT', Journal of Immunology, vol. 156, no. 8, pp. 2716-2722.

The EMT/ITK/TSK (EMT) tyrosine kinase is activated during TCR signaling : LCK is required for optimal activation of EMT. / Gibson, Spencer; August, Avery; Kawakami, Yuko; Kawakami, Toshiaki; Dupont, Bo; Mills, Gordon B.

In: Journal of Immunology, Vol. 156, No. 8, 15.04.1996, p. 2716-2722.

Research output: Contribution to journalArticle

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T1 - The EMT/ITK/TSK (EMT) tyrosine kinase is activated during TCR signaling

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AU - Gibson, Spencer

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N2 - Functional T lymphocyte activation requires concurrent stimulation of the TCR complex and an accessory molecule, most frequently CD28. We have previously demonstrated that the TEC family tyrosine kinase EMT/ITK/TSK (EMT) is activated following cross-linking of CD28. We demonstrate herein that cross-linking of the CD3 component of the TCR complex also leads to EMT activation as indicated by a rapid and transient increase in EMT tyrosine phosphorylation and kinase activity in anti-EMT immunoprecipitates. However, although concurrent cross-linking of the TCR and CD28 results in a marked increase in production of the T cell growth factor IL-2, it does not result in a significant alteration in the magnitude or duration of EMT activation. Somatic cell mutants of the Jurkat T cell line, which lack the SRC family kinase LCK (JCaM1.6), fail to produce IL-2 when stimulated through the TCR complex. EMT activation, as evidenced by increased EMT tyrosine phosphorylation and EMT-associated kinase activity, was also greatly reduced following stimulation of the TCR in the JCaM1.6 Jurkat T cell mutants that lack LCK. In support of a role for LCK in EMT activation, reconstitution of the LCK-negative Jurkat T cell line by enforced expression of LCK restored TCR-mediated EMT activation. Taken together, the data indicate that the EMT tyrosine kinase is activated following cross-linking of the TCR, a process in which LCK likely plays an important role.

AB - Functional T lymphocyte activation requires concurrent stimulation of the TCR complex and an accessory molecule, most frequently CD28. We have previously demonstrated that the TEC family tyrosine kinase EMT/ITK/TSK (EMT) is activated following cross-linking of CD28. We demonstrate herein that cross-linking of the CD3 component of the TCR complex also leads to EMT activation as indicated by a rapid and transient increase in EMT tyrosine phosphorylation and kinase activity in anti-EMT immunoprecipitates. However, although concurrent cross-linking of the TCR and CD28 results in a marked increase in production of the T cell growth factor IL-2, it does not result in a significant alteration in the magnitude or duration of EMT activation. Somatic cell mutants of the Jurkat T cell line, which lack the SRC family kinase LCK (JCaM1.6), fail to produce IL-2 when stimulated through the TCR complex. EMT activation, as evidenced by increased EMT tyrosine phosphorylation and EMT-associated kinase activity, was also greatly reduced following stimulation of the TCR in the JCaM1.6 Jurkat T cell mutants that lack LCK. In support of a role for LCK in EMT activation, reconstitution of the LCK-negative Jurkat T cell line by enforced expression of LCK restored TCR-mediated EMT activation. Taken together, the data indicate that the EMT tyrosine kinase is activated following cross-linking of the TCR, a process in which LCK likely plays an important role.

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Gibson S, August A, Kawakami Y, Kawakami T, Dupont B, Mills GB. The EMT/ITK/TSK (EMT) tyrosine kinase is activated during TCR signaling: LCK is required for optimal activation of EMT. Journal of Immunology. 1996 Apr 15;156(8):2716-2722.