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
N1 - Funding Information:
This is publication number 10495-IMM from the Department of Immunology of The Scripps Research Institute. We thank Dr. S. Cowley for MEK1 cDNA, Dr. R. J. Davis for MKK4 cDNA, and Dr. M. Karin for JNKK1 cDNA. The authors would also like to thank Betty Chastain for excellent secretarial assistance. This work was supported by NIH GM51417 (to J. H.), HL54352 (to G. R. N.), and AI15136 (to R. J. U.), and by AHA Grant-In-Aid 95007690 (to J. H.). This investigation was also supported (in part) by California Division–American Cancer Society Fellowship #2–75–96 (to S. H.). J. H. is an established investigator of the American Heart Association.
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 -