Functional LCK is required for optimal CD28-mediated activation of the TEC family tyrosine kinase EMT/ITK

Spencer Gibson, Avery August, Donald Branch, Bo Dupont, Gordon Mills

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Activation of CD28 on T lymphocytes initiates a cascade of intracellular events, which in concert with activation of the T cell receptor, culminates in production of cytokines and a functional immune response. One of the earliest biochemical changes observed following stimulation of CD28 is tyrosine phosphorylation. We have demonstrated that both the LCK and the EMT/ITK/TSK (EMT) intracellular tyrosine kinases are activated following cross-linking of CD28. Utilizing somatic cell mutants lacking LCK, we demonstrate that functional LCK is required for CD28-induced activation of EMT as evidenced by increased tyrosine phosphorylation and kinase activity. In support of a role for LCK in EMT activation, reconstitution of a LCK- negative Jurkat T cell line by transfection with normal LCK recreates CD28- mediated EMT activation. Furthermore, co-transfection of LCK and EMT into COS-7 cells showed that EMT becomes phosphorylated in the presence of LCK. In addition, increases in EMT association with CD28 were eliminated in a LCK- negative Jurkat cell line, but were restored following transfection of wild type LCK. The data are most compatible with a model in which LCK, either directly or indirectly, initiates EMT activation and association with CD28 following ligation of CD28.

Original languageEnglish (US)
Pages (from-to)7079-7083
Number of pages5
JournalJournal of Biological Chemistry
Volume271
Issue number12
DOIs
StatePublished - Mar 22 1996
Externally publishedYes

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Protein-Tyrosine Kinases
Transfection
Jurkat Cells
Chemical activation
Phosphorylation
T-Lymphocytes
Cell Line
T-cells
COS Cells
T-Cell Antigen Receptor
Ligation
Tyrosine
Association reactions
Cytokines
Phosphotransferases
Cells

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Functional LCK is required for optimal CD28-mediated activation of the TEC family tyrosine kinase EMT/ITK. / Gibson, Spencer; August, Avery; Branch, Donald; Dupont, Bo; Mills, Gordon.

In: Journal of Biological Chemistry, Vol. 271, No. 12, 22.03.1996, p. 7079-7083.

Research output: Contribution to journalArticle

Gibson, Spencer ; August, Avery ; Branch, Donald ; Dupont, Bo ; Mills, Gordon. / Functional LCK is required for optimal CD28-mediated activation of the TEC family tyrosine kinase EMT/ITK. In: Journal of Biological Chemistry. 1996 ; Vol. 271, No. 12. pp. 7079-7083.
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