Apoptosis signaling pathway in T cells is composed of ICE/Ced-3 family proteases and MAP kinase kinase 6b

Shuang Huang, Yong Jiang, Zhuangjie Li, Eisuke Nishida, Patricia Mathias, Shengcai Lin, Richard J. Ulevitch, Glen R. Nemerow, Jiahuai Han

Research output: Contribution to journalArticle

208 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)739-749
Number of pages11
JournalImmunity
Volume6
Issue number6
DOIs
StatePublished - Jun 1997

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Huang, S., Jiang, Y., Li, Z., Nishida, E., Mathias, P., Lin, S., Ulevitch, R. J., Nemerow, G. R., & Han, J. (1997). Apoptosis signaling pathway in T cells is composed of ICE/Ced-3 family proteases and MAP kinase kinase 6b. Immunity, 6(6), 739-749. https://doi.org/10.1016/S1074-7613(00)80449-5