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Evidence for the involvement of tyrosine kinase ZAP 70 in nuclear retinoid receptor-dependent transactivation in T lymphocytes

  1. Author:
    Ishaq, M.
    DeGray, G.
    Natarajan, V.
  2. Author Address

    NCI, Mol Cell Biol Lab, SAIC, NIH, Frederick, MD 21702 USA Ishaq, M, NCI, Mol Cell Biol Lab, SAIC, NIH, Frederick, MD 21702 USA
    1. Year: 2005
    2. Date: OCT 7
  1. Journal: Journal of Biological Chemistry
    1. 280
    2. 40
    3. Pages: 34152-34158
  2. Type of Article: Article
  1. Abstract:

    Retinoic acid receptors (RARs) and retinoid X receptors (RXRs) are transcription factors that control diverse cellular functions during development and homeostasis. The biochemical role of these proteins in T lymphocytes is not well known. Here we have studied the role of protein-tyrosine kinase ZAP70, a key enzyme involved in the proximal signaling events during T cell activation, in the modulation of RXRE- and RARE-dependent activation in T lymphocytes. Surprisingly, ZAP 70-negative Jurkat T cells showed considerable loss of both RXRE- and RARE-mediated transactivation as compared with wild type Jurkat cells. In addition, ZAP 70-negative cells failed to exhibit normal protein kinase C theta and calcineurin-induced transcriptional activity. ZAP 70-negative cells that were reconstituted with active ZAP 70 regained the transactivation function, whereas cells expressing kinase-dead form of ZAP 70 failed to do so. Defective transcriptional activation was also observed in actively proliferating human peripheral blood T lymphocytes in which RNA interference was used to induce loss of ZAP 70 expression. In addition, an Lck-deficient Jurkat cell line that cannot efficiently activate ZAP 70 was also found defective in RXRE- mediated transcription. Finally, RNA interference-induced loss of ZAP 70 or Lck protein in Jurkat cells resulted in significant decrease in the RXRE- dependent activation. Together, these results suggest a novel functional role for ZAP 70 in nuclear receptor-driven transactivation in T lymphocytes

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External Sources

  1. WOS: 000232229700056

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