Phosphorylation-dependent scaffolding role of JSAP1/JIP3 in the ASK1-JNK signaling pathway. A new mode of regulation of the MAP kinase cascade.

JSAP1 (also termed JIP3) is a scaffold protein that interacts with specific components of the JNK signaling pathway. Apoptosis signal-regulating kinase (ASK) 1 is a MAP kinase kinase kinase that activates the JNK and p38 mitogen-activated protein (MAP) kinase cascades in response to environmental stresses such as reactive oxygen species. ...
Here we show that JSAP1 bound ASK1 and enhanced ASK1- and H(2)O(2)-induced JNK activity. ASK1 phosphorylated JSAP1 in vitro and in vivo, and the phosphorylation facilitated interactions of JSAP1 with SEK1/MKK4, MKK7 and JNK3. Furthermore, ASK1-dependent phosphorylation was required for JSAP1 to recruit and thereby activate JNK in response to H(2)O(2). We thus conclude that JSAP1 functions not only as a simple scaffold, but it dynamically participates in signal transduction by forming a phosphorylation-dependent signaling complex in the ASK1-JNK signaling module.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Carrier Proteins, Cell Line, Humans, JNK Mitogen-Activated Protein Kinases, MAP Kinase Kinase Kinase 5, MAP Kinase Kinase Kinases, MAP Kinase Signaling System, Mitogen-Activated Protein Kinases, Nerve Tissue Proteins, Phosphorylation, Protein Binding, Rats, Signal Transduction, Tumor Cells, Cultured
J. Biol. Chem.
Date: Oct. 25, 2002
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