Physiological roles of SAPK/JNK signaling pathway.

Stress-activated protein kinase/c-Jun NH(2)-terminal kinase (SAPK/JNK) is activated by many types of cellular stresses and extracellular signals. Recent studies, including the analysis with knockout mice, have led to progress towards understanding the physiological roles of SAPK/JNK activation in embryonic development in addition to immune responses. SAPK/JNK activation plays essential roles in organogenesis during mouse development by regulating cell survival, apoptosis, and proliferation. Two SAPK/JNK activators, SEK1 and MKK7, are required for fetal liver formation and full activation of SAPK/JNK, which responds to various stimuli in an all-or-none manner. This article focuses on physiological roles of SAPK/JNK activation in fetal liver formation and in apoptosis regulation.

[1]  James E. Ferrell,et al.  The JNK Cascade as a Biochemical Switch in Mammalian Cells Ultrasensitive and All-or-None Responses , 2003, Current Biology.

[2]  J. Ferrell,et al.  Bistability in the JNK cascade , 2001, Current Biology.

[3]  P. Cohen,et al.  Synergistic activation of stress-activated protein kinase 1/c-Jun N-terminal kinase (SAPK1/JNK) isoforms by mitogen-activated protein kinase kinase 4 (MKK4) and MKK7. , 2000, The Biochemical journal.

[4]  E. Wagner,et al.  MKK7 couples stress signalling to G2/M cell-cycle progression and cellular senescence , 2004, Nature Cell Biology.

[5]  T Watanabe,et al.  Impaired Synergistic Activation of Stress-activated Protein Kinase SAPK/JNK in Mouse Embryonic Stem Cells Lacking SEK1/MKK4 , 2001, The Journal of Biological Chemistry.

[6]  T. Katada,et al.  Different Properties of SEK1 and MKK7 in Dual Phosphorylation of Stress-induced Activated Protein Kinase SAPK/JNK in Embryonic Stem Cells* , 2003, The Journal of Biological Chemistry.

[7]  P. Cohen,et al.  Synergistic activation of SAPK1/JNK1 by two MAP kinase kinases in vitro , 1998, Current Biology.

[8]  T. Mak,et al.  Stress-signalling kinase Sek1 protects thymocytes from apoptosis mediated by CD95 and CD3 , 1997, Nature.

[9]  T. Sasaki,et al.  Defective liver formation and liver cell apoptosis in mice lacking the stress signaling kinase SEK1/MKK4. , 1999, Development.

[10]  R. Flavell,et al.  MKK7 is an essential component of the JNK signal transduction pathway activated by proinflammatory cytokines. , 2001, Genes & development.

[11]  T. Katada,et al.  Activation mechanism and physiological roles of stress-activated protein kinase/c-Jun NH2-terminal kinase in mammalian cells. , 2003, Journal of biological regulators and homeostatic agents.

[12]  R. Flavell,et al.  Targeted disruption of the MKK4 gene causes embryonic death, inhibition of c-Jun NH2-terminal kinase activation, and defects in AP-1 transcriptional activity. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[13]  R. Davis,et al.  Signal Transduction by the JNK Group of MAP Kinases , 2000, Cell.

[14]  A. Manning,et al.  Targeting JNK for therapeutic benefit: from junk to gold? , 2003, Nature Reviews Drug Discovery.

[15]  P. Griffin,et al.  Activation of JNK3 alpha 1 requires both MKK4 and MKK7: kinetic characterization of in vitro phosphorylated JNK3 alpha 1. , 2000, Biochemistry.

[16]  T. Mak,et al.  SEK1/MKK4-mediated SAPK/JNK signaling participates in embryonic hepatoblast proliferation via a pathway different from NF-kappaB-induced anti-apoptosis. , 2002, Developmental biology.

[17]  L. Zon,et al.  SEK1 deficiency reveals mitogen-activated protein kinase cascade crossregulation and leads to abnormal hepatogenesis. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[18]  Teiji Wada,et al.  Mitogen-activated protein kinases in apoptosis regulation , 2004, Oncogene.

[19]  D. Bar-Sagi,et al.  Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway. , 2000, Science.

[20]  T. Mak,et al.  Stress Induces Mitochondria-mediated Apoptosis Independent of SAPK/JNK Activation in Embryonic Stem Cells* , 2004, Journal of Biological Chemistry.

[21]  P. Rakic,et al.  The Jnk1 and Jnk2 Protein Kinases Are Required for Regional Specific Apoptosis during Early Brain Development , 1999, Neuron.

[22]  C. Weston,et al.  The JNK signal transduction pathway. , 2007, Current opinion in genetics & development.

[23]  M. Karin,et al.  Mammalian MAP kinase signalling cascades , 2001, Nature.

[24]  A. Lin Activation of the JNK signaling pathway: Breaking the brake on apoptosis , 2003, BioEssays : news and reviews in molecular, cellular and developmental biology.