Apoptosis Signaling Pathway in T Cells Is Composed of ICE/Ced-3 Family Proteases and MAP Kinase Kinase 6b

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. MKK6...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 1997-06, Vol.6 (6), p.739-749
Main Authors: Huang, Shuang, Jiang, Yong, Li, Zhuangjie, Nishida, Eisuke, Mathias, Patricia, Lin, Shengcai, Ulevitch, Richard J, Nemerow, Glen R, Han, Jiahuai
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Apoptosis
Caenorhabditis elegans Proteins
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
Calcium-Calmodulin-Dependent Protein Kinases - physiology
Caspase 3
Caspases
Cysteine Endopeptidases - physiology
Enzyme Activation
fas Receptor - physiology
Humans
MAP Kinase Kinase 6
Mitogen-Activated Protein Kinases
Molecular Sequence Data
p38 Mitogen-Activated Protein Kinases
Sequence Alignment
Sequence Homology, Amino Acid
Signal Transduction
Structure-Activity Relationship
T-Lymphocytes - cytology
T-Lymphocytes - enzymology
Tumor Cells, Cultured
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Summary: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/Ced-3 family of proteases and leads to cell death. These studies represent a demonstration of an apoptotic pathway that is comprised of both the ICE/Ced-3 family of proteases and MAP kinase kinase 6.
ISSN:1074-7613
1097-4180
DOI:10.1016/S1074-7613(00)80449-5