TY - JOUR
T1 - Apoptosis signaling pathway in T cells is composed of ICE/Ced-3 family proteases and MAP kinase kinase 6b
AU - Huang, Shuang
AU - Jiang, Yong
AU - Li, Zhuangjie
AU - Nishida, Eisuke
AU - Mathias, Patricia
AU - Lin, Shengcai
AU - Ulevitch, Richard J.
AU - Nemerow, Glen R.
AU - Han, Jiahuai
PY - 1997/6
Y1 - 1997/6
N2 - Fas/APO-1(CD95) ligation activates programmed cell death, a cellular process that plays an important role in the maturation of the host immune response. We show that activation of a specific MAP kinase kinase (MKK), MKK6b, is necessary and sufficient for Fas-induced apoptosis of Jurkat T cells. MKK6b activation occurs downstream of an interleukin-1 converting enzyme-like (ICE-like) protease(s), while execution of the apoptotic pathway by MKK6b requires both ICE- and CPP32-like proteases. Surprisingly, the p38 MAP kinase protein, a known substrate of MKK6b, does not participate in Fas/MKK6b-mediated apoptosis. These findings indicate a divergence of the MKK6b signaling pathways, one of which activates p38 and leads to regulation of gene expression, and one of which activates the ICE/Cad-3 family of proteases and leads to cell death. These studios represent a demonstration of an apoptotic pathway that is comprised of both the ICF/Ced-3 family of proteases and MAP kinase kinase 6.
AB - Fas/APO-1(CD95) ligation activates programmed cell death, a cellular process that plays an important role in the maturation of the host immune response. We show that activation of a specific MAP kinase kinase (MKK), MKK6b, is necessary and sufficient for Fas-induced apoptosis of Jurkat T cells. MKK6b activation occurs downstream of an interleukin-1 converting enzyme-like (ICE-like) protease(s), while execution of the apoptotic pathway by MKK6b requires both ICE- and CPP32-like proteases. Surprisingly, the p38 MAP kinase protein, a known substrate of MKK6b, does not participate in Fas/MKK6b-mediated apoptosis. These findings indicate a divergence of the MKK6b signaling pathways, one of which activates p38 and leads to regulation of gene expression, and one of which activates the ICE/Cad-3 family of proteases and leads to cell death. These studios represent a demonstration of an apoptotic pathway that is comprised of both the ICF/Ced-3 family of proteases and MAP kinase kinase 6.
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U2 - 10.1016/S1074-7613(00)80449-5
DO - 10.1016/S1074-7613(00)80449-5
M3 - Article
C2 - 9208846
AN - SCOPUS:0030812347
VL - 6
SP - 739
EP - 749
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 6
ER -