Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways

H Ichijo; E Nishida; K Irie; P ten Dijke; M Saitoh; T Moriguchi; M Takagi; K Matsumoto; K Miyazono; Y Gotoh

doi:10.1126/science.275.5296.90

Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways

Science. 1997 Jan 3;275(5296):90-4. doi: 10.1126/science.275.5296.90.

Authors

H Ichijo¹, E Nishida, K Irie, P ten Dijke, M Saitoh, T Moriguchi, M Takagi, K Matsumoto, K Miyazono, Y Gotoh

Affiliation

¹ Department of Biochemistry, The Cancer Institute, Tokyo, Japanese Foundation for Cancer Research, 1-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo 170, Japan.

PMID: 8974401
DOI: 10.1126/science.275.5296.90

Abstract

Mitogen-activated protein (MAP) kinase cascades are activated in response to various extracellular stimuli, including growth factors and environmental stresses. A MAP kinase kinase kinase (MAPKKK), termed ASK1, was identified that activated two different subgroups of MAP kinase kinases (MAPKK), SEK1 (or MKK4) and MKK3/MAPKK6 (or MKK6), which in turn activated stress-activated protein kinase (SAPK, also known as JNK; c-Jun amino-terminal kinase) and p38 subgroups of MAP kinases, respectively. Overexpression of ASK1 induced apoptotic cell death, and ASK1 was activated in cells treated with tumor necrosis factor-alpha (TNF-alpha). Moreover, TNF-alpha-induced apoptosis was inhibited by a catalytically inactive form of ASK1. ASK1 may be a key element in the mechanism of stress- and cytokine-induced apoptosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Apoptosis*
COS Cells
Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
Cell Division
Cell Line
Cell Survival
Enzyme Activation
JNK Mitogen-Activated Protein Kinases
MAP Kinase Kinase 6
MAP Kinase Kinase Kinases
Mitogen-Activated Protein Kinase Kinases*
Mitogen-Activated Protein Kinases*
Molecular Sequence Data
Phosphorylation
Polymerase Chain Reaction
Protein Serine-Threonine Kinases / chemistry
Protein Serine-Threonine Kinases / metabolism*
Protein-Tyrosine Kinases / metabolism
Recombinant Proteins / metabolism
Saccharomyces cerevisiae / genetics
Saccharomyces cerevisiae / growth & development
Saccharomyces cerevisiae / metabolism
Signal Transduction*
Transfection
Tumor Necrosis Factor-alpha / pharmacology
p38 Mitogen-Activated Protein Kinases

Substances

Recombinant Proteins
Tumor Necrosis Factor-alpha
Protein-Tyrosine Kinases
Protein Serine-Threonine Kinases
Calcium-Calmodulin-Dependent Protein Kinases
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases
p38 Mitogen-Activated Protein Kinases
MAP Kinase Kinase Kinases
MAP Kinase Kinase 6
Mitogen-Activated Protein Kinase Kinases

Associated data

GENBANK/D84476