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Evidence for the Involvement of Tyrosine Kinase ZAP 70 in Nuclear Retinoid Receptor-Dependent Transactivation in T Lymphocytes

Evidence for the Involvement of Tyrosine Kinase ZAP 70 in Nuclear Retinoid Receptor-Dependent Transactivation in T Lymphocytes

Mohammad Ishaq, Gerald DeGray, Ven Natarajan

J Biol Chem. 2005 Oct 7;280(40):34152-8.

PMID: 16096284

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 ZAP 70, 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 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42411991	ZAP-70 Tyrosine Kinase human			Price

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