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T cell activation up-regulates the expression of the focal adhesion kinase Pyk2: opposing roles for the activation of protein kinase C and the increase in intracellular Ca2+.

Publication ,  Journal Article
Tsuchida, M; Manthei, ER; Alam, T; Knechtle, SJ; Hamawy, MM
Published in: J Immunol
December 15, 1999

T cell activation initiates signals that control gene expression of molecules important for T cell function. The focal adhesion kinase Pyk2 has been implicated in T cell signaling. To further analyze the involvement of Pyk2 in T cell processes, we examined the effect of T cell stimulation on the expression of Pyk2. We found that TCR ligation or PMA increased Pyk2 expression in Jurkat T cells and in normal T cells. In contrast, TCR ligation and PMA failed to induce any detectable increase in the expression of the other member of the focal adhesion kinase family, Fak, in Jurkat T cells and induced only a weak increase in Fak expression in normal T cells. The serine/threonine kinases, protein kinase C and mitogen-activated protein/extracellular signal-related kinase kinase (MEK), regulated Pyk2 expression, as inhibitors of these kinases blocked stimulus-induced Pyk2 expression. Cyclosporin A, FK506, and KN-62 did not block Pyk2 expression; thus, calcineurin and Ca2+/calmodulin-activated kinases are not critical for augmenting Pyk2 expression. TCR ligation increased Pyk2 mRNA, and the transcriptional inhibitor actinomycin D blocked Pyk2 expression. Strikingly, Ca2+ ionophores, at concentrations that in combination with other stimuli induced IL-2 expression, blocked TCR- and PMA-induced up-regulation of Pyk2 expression. Thus, the increase in Ca2+ has opposing effects on IL-2 and Pyk2 expression. Cyclosporin A and FK506, but not KN-62, blocked Ca2+ ionophore-mediated inhibition of Pyk2 expression, implicating calcineurin in down-regulating Pyk2 expression. These results show that TCR-triggered intracellular signals increase Pyk2 expression and shed light on the molecular mechanisms that regulate Pyk2 expression in T cells.

Duke Scholars

Published In

J Immunol

ISSN

0022-1767

Publication Date

December 15, 1999

Volume

163

Issue

12

Start / End Page

6640 / 6650

Location

United States

Related Subject Headings

  • Up-Regulation
  • Transcription, Genetic
  • Tetradecanoylphorbol Acetate
  • Tacrolimus
  • T-Lymphocytes
  • Signal Transduction
  • Receptors, Antigen, T-Cell
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
  • Protein Kinase C
 

Published In

J Immunol

ISSN

0022-1767

Publication Date

December 15, 1999

Volume

163

Issue

12

Start / End Page

6640 / 6650

Location

United States

Related Subject Headings

  • Up-Regulation
  • Transcription, Genetic
  • Tetradecanoylphorbol Acetate
  • Tacrolimus
  • T-Lymphocytes
  • Signal Transduction
  • Receptors, Antigen, T-Cell
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
  • Protein Kinase C