Stress-signalling kinase Sek1 protects thymocytes from apoptosis mediated by CD95 and CD3

来自 EBSCO

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作者：

H Nishina，KD Fischer，L Radvanyi，A Shahinian，R Hakem，EA Rubie，A Bernstein，TW Mak，JR Woodgett，JM Penninger

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摘要：

Distinct and evolutionarily conserved signal transduction cascades mediate survival or death in response to developmental and environmental cues. The stress-activated protein kinases, or Jun N-terminal kinases (SAPKs/JNKs), are activated in response to a variety of cellular stresses such as changes in osmolarity and metabolism, DNA damage, heat shock, ischaemia, or inflammatory cytokines. Sek1 (JNKK/MKK4) is a direct activator of SAPKs/JNKs in response to environmental stresses or mitogenic factors. Here we investigate the role of Sek1 in development and apoptosis by deletingin embryonic stem (ES) cells by homologous recombination. We provide genetic evidence that different stresses utilize distinct signalling pathways for SAPK/ JNK activation,/chimaeric mice have normal numbers of mature T cells but fewer immature CD4CD8thymocytes. Themutation did not affect the induction of apoptosis in response to environmental stresses in ES and T cells: instead,protected thymocytes from CD95 (Fas)- and CD3-mediated apoptosis. These data indicate that SEK1 mediates survival signals in T-cell development.

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关键词：

Animals Antigens, CD3 physiology Antigens, CD95 physiology Apoptosis physiology Ca(2+)-Calmodulin Dependent Protein Kinase metabolism Cell Differentiation physiology Cell Line Chimera DNA-Binding Proteins Enzyme Activation Gene Deletion Gene Targeting JNK Mitogen-Activated Protein Kinases MAP Kinase Kinase 4 Mice Mitogen-Activated Protein Kinase Kinases Mitogen-Activated Protein Kinases Protein Kinases genetics physiology Proteins genetics metabolism Research Support, Non-U.S. Gov't Stem Cells T-Lymphocytes cytology Thymus Gland cytology