PMID- 10021384
OWN - NLM
STAT- MEDLINE
DCOM- 19990330
LR  - 20190728
IS  - 0960-9822 (Print)
IS  - 0960-9822 (Linking)
VI  - 9
IP  - 3
DP  - 1999 Feb 11
TI  - JNK2 is required for efficient T-cell activation and apoptosis but not for normal
      lymphocyte development.
PG  - 116-25
AB  - BACKGROUND: The Jun N-terminal kinase (JNK) signaling pathway has been implicated
      in cell proliferation and apoptosis, but its function seems to depend on the cell
      type and inducing signal. In T cells, JNK has been implicated in both
      antigen-induced activation and apoptosis. RESULTS: We generated mice lacking the 
      JNK2 isozymes. The mutant mice were healthy and fertile but defective in
      peripheral T-cell activation induced by antibody to the CD3 component of the
      T-cell receptor (TCR) complex - proliferation and production of interleukin-2
      (IL-2), IL-4 and interferon-gamma (IFN-gamma) were reduced. The proliferation
      defect was restored by exogenous IL-2. B-cell activation was normal in the
      absence of JNK2. Activation-induced peripheral T-cell apoptosis was comparable
      between mutant and wild-type mice, but immature (CD4(+) CD8(+)) thymocytes
      lacking JNK2 were resistant to apoptosis induced by administration of anti-CD3
      antibody in vivo. The lack of JNK2 also resulted in partial resistance of
      thymocytes to anti-CD3 antibody in vitro, but had little or no effect on
      apoptosis induced by anti-Fas antibody, dexamethasone or ultraviolet-C (UVC)
      radiation. CONCLUSIONS: JNK2 is essential for efficient activation of peripheral 
      T cells but not B cells. Peripheral T-cell activation is probably required
      indirectly for induction of thymocyte apoptosis resulting from administration of 
      anti-CD3 antibody in vivo. JNK2 functions in a cell-type-specific and
      stimulus-dependent manner, being required for apoptosis of immature thymocytes
      induced by anti-CD3 antibody but not for apoptosis induced by anti-Fas antibody, 
      UVC or dexamethasone. JNK2 is not required for activation-induced cell death of
      mature T cells.
FAU - Sabapathy, K
AU  - Sabapathy K
AD  - Research Institute for Molecular Pathology, Vienna, Austria.
FAU - Hu, Y
AU  - Hu Y
FAU - Kallunki, T
AU  - Kallunki T
FAU - Schreiber, M
AU  - Schreiber M
FAU - David, J P
AU  - David JP
FAU - Jochum, W
AU  - Jochum W
FAU - Wagner, E F
AU  - Wagner EF
FAU - Karin, M
AU  - Karin M
LA  - eng
GR  - ES04151/ES/NIEHS NIH HHS/United States
GR  - ES06376/ES/NIEHS NIH HHS/United States
GR  - HL35018/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Curr Biol
JT  - Current biology : CB
JID - 9107782
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Isoenzymes)
RN  - 0 (Muromonab-CD3)
RN  - 0 (fas Receptor)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.24 (Mitogen-Activated Protein Kinase 9)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/immunology/pharmacology
MH  - *Apoptosis
MH  - B-Lymphocytes/immunology
MH  - Dexamethasone/pharmacology
MH  - Drug Resistance
MH  - Gene Targeting
MH  - Isoenzymes/deficiency/genetics/*physiology
MH  - *Lymphocyte Activation/drug effects/radiation effects
MH  - Mice
MH  - Mice, Knockout
MH  - Mitogen-Activated Protein Kinase 9
MH  - *Mitogen-Activated Protein Kinases
MH  - Muromonab-CD3/pharmacology
MH  - Protein Kinases/deficiency/genetics/*physiology
MH  - RNA Splicing
MH  - T-Lymphocytes/cytology/*enzymology/immunology
MH  - Ultraviolet Rays
MH  - fas Receptor/immunology
EDAT- 1999/02/18 00:00
MHDA- 1999/02/18 00:01
CRDT- 1999/02/18 00:00
PHST- 1999/02/18 00:00 [pubmed]
PHST- 1999/02/18 00:01 [medline]
PHST- 1999/02/18 00:00 [entrez]
AID - S0960-9822(99)80065-7 [pii]
AID - 10.1016/s0960-9822(99)80065-7 [doi]
PST - ppublish
SO  - Curr Biol. 1999 Feb 11;9(3):116-25. doi: 10.1016/s0960-9822(99)80065-7.