Residues of the CD28 cytoplasmic tail required for the activation of protein tyrosine kinases and the induction of IL-2 secretion

J. M.C. Tenp, P. D. King, A. Sadra, X. R. Liu, A. Han, A. Selvakumar, A. August, B. Dupont

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The structural requirements of the CD28 cytoplasmic tail necessary for activation of protein tyrosine kinases, phosphatidylinositol 3-kinase (PI 3-kinase) and IL-2 production were investigated in Jurkat T cells. A series of CD8-CD28 chimeric receptors consisting of CD8 alpha linked to different mutated versions of the human CD28 cytoplasmic tail were constructed and transfected into Jurkat T cells. This included substitutions of each of the four tyrosines (Y173, 188, 191 and 200), to phenylalanine alone or in combination. In addition, five truncation mutations were also analyzed. Our results indicate that phosphorylation of tyrosines in the CD28 cytoplasmic tail is not necessary for the activation of the kinases LCK and ITK, although for ITK activation some contribution of phosphorylation of tyrosine 173 is evident. Both kinases are controlled by residues contained within the first half of the tail. Phosphorylation of tyrosine 173, and hence PI 3-kinase activation, is not required for the induction of IL-2 in Jurkat cells. By contrast, phosphorylation of each of the remaining three tyrosines of the CD28 cytoplasmic tail is essential for IL-2 secretion. Evidence is presented that in vitro, ITK, but not LCK, can phosphorylate these remaining three tyrosines. Together with the finding that in an LCK negative variant of Jurkat, JCAM1.6, CD28 plus PMA mediated activation of ITK correlates with the induction of IL-2, this suggests an important role for ITK in this response. NIH-CA09149, CA225Ü7, CA08748 and AI37294.

Original languageEnglish (US)
Pages (from-to)A1451
JournalFASEB Journal
Issue number6
StatePublished - 1996

All Science Journal Classification (ASJC) codes

  • Genetics
  • Molecular Biology
  • Biochemistry
  • Biotechnology


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