PMID- 10196263
OWN - NLM
STAT- MEDLINE
DCOM- 19990519
LR  - 20200724
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 73
IP  - 5
DP  - 1999 May
TI  - Altered expression of tyrosine kinases of the Src and Syk families in human
      T-cell leukemia virus type 1-infected T-cell lines.
PG  - 3709-17
AB  - During the late phase of adult T-cell leukemia/lymphoma, a severe
      lymphoproliferative disorder caused by human T-cell leukemia virus type 1
      (HTLV-1), leukemic cells no longer produce interleukin-2. Several studies have
      reported the lack of the Src-like protein tyrosine kinase Lck and overexpression 
      of Lyn and Fyn in these cells. In this report we demonstrate that, in addition to
      the downregulation of TCR, CD45, and Lck (which are key components of T-cell
      activation), HTLV-1-infected cell lines demonstrate a large increase of FynB, a
      Fyn isoform usually poorly expressed in T cells. Furthermore, similar to anergic 
      T cells, Fyn is hyperactive in one of these HTLV-1-infected T-cell lines,
      probably as a consequence of Csk downregulation. A second family of two proteins,
      Zap-70 and Syk, relay the signal of T-cell activation. We demonstrate that in
      contrast to uninfected T cells, Zap-70 is absent in HTLV-1-infected T cells,
      whereas Syk is overexpressed. In searching for the mechanism responsible for FynB
      overexpression and Zap-70 downregulation, we have investigated the ability of the
      Tax and Rex proteins to modulate Zap-70 expression and the alternative splicing
      mechanism which gives rise to either FynB or FynT. By using Jurkat T cells stably
      transfected with the tax and rex genes or inducibly expressing the tax gene, we
      found that the expression of Rex was necessary to increase fynB expression,
      suggesting that Rex controls fyn gene splicing. Conversely, with the same Jurkat 
      clones, we found that the expression of Tax but not Rex could downregulate Zap-70
      expression. These results suggest that the effect of Tax and Rex must cooperate
      to deregulate the pathway of T-cell activation in HTLV-1-infected T cells.
FAU - Weil, R
AU  - Weil R
AD  - Unite de Biologie Moleculaire de l'Expression Genique, URA 1773 Centre National
      de la Recherche Scientifique, 75724 Paris Cedex 15, France. rweil@pasteur.fr
FAU - Levraud, J P
AU  - Levraud JP
FAU - Dodon, M D
AU  - Dodon MD
FAU - Bessia, C
AU  - Bessia C
FAU - Hazan, U
AU  - Hazan U
FAU - Kourilsky, P
AU  - Kourilsky P
FAU - Israel, A
AU  - Israel A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Interleukin-2)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (TYRO3 protein, human)
RN  - EC 2.7.10.2 (FYN protein, human)
RN  - EC 2.7.10.2 (Lymphocyte Specific Protein Tyrosine Kinase p56(lck))
RN  - EC 2.7.10.2 (Proto-Oncogene Proteins c-fyn)
RN  - EC 2.7.10.2 (ZAP-70 Protein-Tyrosine Kinase)
RN  - EC 2.7.10.2 (ZAP70 protein, human)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - EC 3.1.3.48 (Leukocyte Common Antigens)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 1)
SB  - IM
MH  - Down-Regulation
MH  - Human T-lymphotropic virus 1/*physiology
MH  - Humans
MH  - Interleukin-2/metabolism
MH  - Jurkat Cells
MH  - Leukocyte Common Antigens/biosynthesis
MH  - Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/biosynthesis
MH  - Phosphorylation
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 1
MH  - Protein-Tyrosine Kinases/biosynthesis
MH  - Proto-Oncogene Proteins/biosynthesis
MH  - Proto-Oncogene Proteins c-fyn
MH  - Receptor Protein-Tyrosine Kinases/*biosynthesis
MH  - Receptors, Antigen, T-Cell/biosynthesis
MH  - Tumor Cells, Cultured
MH  - ZAP-70 Protein-Tyrosine Kinase
MH  - src-Family Kinases/*biosynthesis
PMC - PMC104146
EDAT- 1999/04/10 00:00
MHDA- 1999/04/10 00:01
CRDT- 1999/04/10 00:00
PHST- 1999/04/10 00:00 [pubmed]
PHST- 1999/04/10 00:01 [medline]
PHST- 1999/04/10 00:00 [entrez]
AID - 10.1128/JVI.73.5.3709-3717.1999 [doi]
PST - ppublish
SO  - J Virol. 1999 May;73(5):3709-17. doi: 10.1128/JVI.73.5.3709-3717.1999.