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 Journal Article


Authors: August, A.; Gibson, S.; Kawakami, Y.; Kawakami, T.; Mills, G. B.; Dupont, B.
Article 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: signal transduction; protein phosphorylation; human cell; enzyme activation; protein tyrosine kinase; monoclonal antibody; t lymphocyte receptor; lymphocyte activation; immunoprecipitation; immunoblotting; cell stimulation; tyrosine kinase; enzyme assay; t lymphocyte activation; cd28 antigen; leukemia cell line; costimulation; human; priority journal; article; vav
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 91
Issue: 20
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 1994-09-27
Start Page: 9347
End Page: 9351
Language: English
DOI: 10.1073/pnas.91.20.9347
PROVIDER: scopus
PMCID: PMC44809
PUBMED: 7524075
DOI/URL:
Notes: Export Date: 14 January 2019 -- Article -- CODEN: PNASA C2 -- Source: Scopus
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  1. Bo Dupont
    264 Dupont