TY - JOUR
T1 - Disruption of Mekk2 in mice reveals an unexpected role for MEKK2 in modulating T-cell receptor signal transduction
AU - Guo, Zijian
AU - Clydesdale, Gavin
AU - Cheng, Jinke
AU - Kim, Kihwan
AU - Gan, Lin
AU - McConkey, David J.
AU - Ullrich, Stephen E.
AU - Zhuang, Yuan
AU - Su, Bing
PY - 2002
Y1 - 2002
N2 - MEKK2 is a member of the mitogen-activated protein kinase (MAPK) kinase kinase gene family involved in regulating multiple MAPK signaling pathways. To elucidate the in vivo function of MEKK2, we generated mice carrying a targeted mutation in the Mekk2 locus. Mekk2-/- mice are viable and fertile. Major subsets of thymic and spleen T cells in Mekk2-deficient mice were indistinguishable from those in wild-type mice. B-cell development appeared to proceed similarly in the bone marrow of Mekk2-deficient and wild-type mice. However, Mekk2-/- T-cell proliferation was augmented in response to anti-CD3 monoclonal antibody (MAb) stimulation, and these T cells produced more interleukin 2 and gamma interferon than did the wild-type T cells, suggesting that MEKK2 may be involved in controlling the strength of T-cell receptor (TCR) signaling. Consistently, Mekk2-/- thymocytes were more susceptible than wild-type thymocytes to anti-CD3 MAb-induced cell death. Furthermore, TCR-mediated c-Jun N-terminal kinase activation was not blocked but moderately enhanced in Mekk2-/- T cells. Neither extracellular signal-regulated kinase nor p38 MAPK activation was affected in Mekk2-/- T cells. In conclusion, we found that MEKK2 may be required for controlling the strength of TCR/CD3 signaling.
AB - MEKK2 is a member of the mitogen-activated protein kinase (MAPK) kinase kinase gene family involved in regulating multiple MAPK signaling pathways. To elucidate the in vivo function of MEKK2, we generated mice carrying a targeted mutation in the Mekk2 locus. Mekk2-/- mice are viable and fertile. Major subsets of thymic and spleen T cells in Mekk2-deficient mice were indistinguishable from those in wild-type mice. B-cell development appeared to proceed similarly in the bone marrow of Mekk2-deficient and wild-type mice. However, Mekk2-/- T-cell proliferation was augmented in response to anti-CD3 monoclonal antibody (MAb) stimulation, and these T cells produced more interleukin 2 and gamma interferon than did the wild-type T cells, suggesting that MEKK2 may be involved in controlling the strength of T-cell receptor (TCR) signaling. Consistently, Mekk2-/- thymocytes were more susceptible than wild-type thymocytes to anti-CD3 MAb-induced cell death. Furthermore, TCR-mediated c-Jun N-terminal kinase activation was not blocked but moderately enhanced in Mekk2-/- T cells. Neither extracellular signal-regulated kinase nor p38 MAPK activation was affected in Mekk2-/- T cells. In conclusion, we found that MEKK2 may be required for controlling the strength of TCR/CD3 signaling.
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U2 - 10.1128/MCB.22.16.5761-5768.2002
DO - 10.1128/MCB.22.16.5761-5768.2002
M3 - Article
C2 - 12138187
AN - SCOPUS:0036315121
SN - 0270-7306
VL - 22
SP - 5761
EP - 5768
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 16
ER -