PMID- 16096284
OWN - NLM
STAT- MEDLINE
DCOM- 20051202
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 280
IP  - 40
DP  - 2005 Oct 7
TI  - Evidence for the involvement of tyrosine kinase ZAP 70 in nuclear retinoid 
      receptor-dependent transactivation in T lymphocytes.
PG  - 34152-8
AB  - 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.
FAU - Ishaq, Mohammad
AU  - Ishaq M
AD  - Laboratory of Molecular Cell Biology, SAIC, NCI-Frederick, National Institutes of 
      Health, Frederick, Maryland 21702, USA. mishaq@nih.gov
FAU - DeGray, Gerald
AU  - DeGray G
FAU - Natarajan, Ven
AU  - Natarajan V
LA  - eng
GR  - N01-CO-12400/CO/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20050810
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Retinoid X Receptors)
RN  - EC 2.7.10.2 (ZAP-70 Protein-Tyrosine Kinase)
SB  - IM
MH  - Humans
MH  - Jurkat Cells
MH  - Lymphocyte Activation
MH  - Retinoid X Receptors/*physiology
MH  - T-Lymphocytes/*enzymology/physiology
MH  - ZAP-70 Protein-Tyrosine Kinase/*metabolism
EDAT- 2005/08/13 09:00
MHDA- 2005/12/13 09:00
CRDT- 2005/08/13 09:00
PHST- 2005/08/13 09:00 [pubmed]
PHST- 2005/12/13 09:00 [medline]
PHST- 2005/08/13 09:00 [entrez]
AID - S0021-9258(20)79003-4 [pii]
AID - 10.1074/jbc.M501547200 [doi]
PST - ppublish
SO  - J Biol Chem. 2005 Oct 7;280(40):34152-8. doi: 10.1074/jbc.M501547200. Epub 2005 
      Aug 10.