title: Apoptosis signaling pathway in T cells is composed of ICE/Ced-3 family proteases and MAP kinase kinase 6b.
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/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.
authors.affiliation: Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: S
authors.initials: S
authors.lastname: Huang
authors.forename: Y
authors.initials: Y
authors.lastname: Jiang
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: E
authors.initials: E
authors.lastname: Nishida
authors.forename: P
authors.initials: P
authors.lastname: Mathias
authors.forename: S
authors.initials: S
authors.lastname: Lin
authors.forename: R J
authors.initials: RJ
authors.lastname: Ulevitch
authors.forename: G R
authors.initials: GR
authors.lastname: Nemerow
authors.forename: J
authors.initials: J
authors.lastname: Han
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis; D029742:Caenorhabditis elegans Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases / Q000502:physiology*; D004789:Enzyme Activation; D006801:Humans; D048669:MAP Kinase Kinase 6; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000166:cytology* / Q000201:enzymology; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D029742:Caenorhabditis elegans Proteins; D019014:fas Receptor; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048669:MAP Kinase Kinase 6; C482566:MAP2K6 protein, human; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; C089223:ced-3 protein, C elegans