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

Immunity. 1997 Jun;6(6):739-49. doi: 10.1016/s1074-7613(00)80449-5.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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
  • Humans
  • MAP Kinase Kinase 6
  • Mitogen-Activated Protein Kinases*
  • Molecular Sequence Data
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Structure-Activity Relationship
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / enzymology
  • Tumor Cells, Cultured
  • fas Receptor / physiology*
  • p38 Mitogen-Activated Protein Kinases


  • Caenorhabditis elegans Proteins
  • fas Receptor
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 6
  • MAP2K6 protein, human
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • Cysteine Endopeptidases
  • ced-3 protein, C elegans