Involvement of ASK1 in Ca2+-induced p38 MAP kinase activation.
The mammalian mitogen-activated protein (MAP) kinase kinase kinase apoptosis signal-regulating kinase 1 (ASK1) is a pivotal component in cytokine- and stress-induced apoptosis. It also regulates cell differentiation and survival through p38 MAP kinase activation. Here we show that Ca2+ signalling regulates the ASK1-p38 MAP kinase cascade. Ca2+ influx evoked by membrane depolarization in primary neurons and synaptosomes induced activation of p38, which was impaired in those derived from ASK1-deficient mice. Ca2+/calmodulin-dependent protein kinase type II (CaMKII) activated ASK1 by phosphorylation. Moreover, p38 activation induced by the expression of constitutively active CaMKII required endogenous ASK1. Thus, ASK1 is a critical intermediate of Ca2+ signalling between CaMKII and p38 MAP kinase.
Takeda
Kohsuke
K
Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, and CREST, Japan Science and Technology Corporation, Hongo, Tokyo, Japan.
Matsuzawa
Atsushi
A
Nishitoh
Hideki
H
Tobiume
Kei
K
Kishida
Satoshi
S
Ninomiya-Tsuji
Jun
J
Matsumoto
Kunihiro
K
Ichijo
Hidenori
H
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D020013:Calcium Signaling; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005982:Glutathione Transferase / Q000032:analysis; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008387:Marine Toxins / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D035964:Oxocins / Q000494:pharmacology; D010766:Phosphorylation; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D000095702:Polyether Toxins
D002118:Calcium; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D005982:Glutathione Transferase; D048848:MAP Kinase Kinase Kinase 5; D008387:Marine Toxins; D035964:Oxocins; D024681:Potassium Channels, Calcium-Activated; D034741:RNA, Small Interfering; D048051:p38 Mitogen-Activated Protein Kinases; C020394:maitotoxin; D000095702:Polyether Toxins