Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Calcium / metabolism
-
Calcium / pharmacology
-
Calcium Signaling*
-
Calcium-Calmodulin-Dependent Protein Kinase Type 2
-
Calcium-Calmodulin-Dependent Protein Kinases / metabolism
-
Cells, Cultured
-
Fibroblasts / drug effects
-
Fibroblasts / metabolism
-
Glutathione Transferase / analysis
-
MAP Kinase Kinase Kinase 5 / metabolism
-
MAP Kinase Kinase Kinase 5 / physiology*
-
MAP Kinase Signaling System / physiology
-
Marine Toxins / pharmacology
-
Mice
-
Mice, Inbred C57BL
-
Oxocins / pharmacology
-
Phosphorylation
-
Potassium Channels, Calcium-Activated / metabolism
-
RNA, Small Interfering / pharmacology
-
Synaptosomes / drug effects
-
Synaptosomes / metabolism
-
p38 Mitogen-Activated Protein Kinases / metabolism*
Substances
-
Marine Toxins
-
Oxocins
-
Potassium Channels, Calcium-Activated
-
RNA, Small Interfering
-
maitotoxin
-
Glutathione Transferase
-
Calcium-Calmodulin-Dependent Protein Kinase Type 2
-
Calcium-Calmodulin-Dependent Protein Kinases
-
p38 Mitogen-Activated Protein Kinases
-
MAP Kinase Kinase Kinase 5
-
Calcium