A scaffold protein in the c-Jun NH2-terminal kinase signaling pathways suppresses the extracellular signal-regulated kinase signaling pathways

Yoshihide Kuboki, Michihiko Ito, Nobuhiko Takamatsu, Ken-ichi Yamamoto, Tadayoshi Shiba, Katsuji Yoshioka

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

We previously reported that c-Jun NH2-terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1) functions as a putative scaffold factor in the JNK mitogen-activated protein kinase (MAPK) cascades. In that study we also found MEK1 and Raf-1, which are involved in the extracellular signal-regulated kinase (ERK) MAPK cascades, bind to JSAP1. Here we have defined the regions of JSAP1 responsible for the interactions with MEK1 and Raf-1. Both of the binding regions were mapped to the COOH-terminal region (residues 1054-1305) of JSAP1. We next examined the effect of overexpressing JSAP1 on the activation of ERK by phorbol 12-myristate 13-acetate in transfected COS-7 cells and found that JSAP1 inhibits ERK's activation and that the COOH-terminal region of JSAP1 was required for the inhibition. Finally, we investigated the molecular mechanism of JSAP1's inhibitory function and showed that JSAP1 prevents MEK1 phosphorylation and activation by Raf-1, resulting in the suppression of the activation of ERK. Taken together, these results suggest that JSAP1 is involved both in the JNK cascades, as a scaffolding factor, and the ERK cascades, as a suppressor.

Original languageEnglish
Pages (from-to)39815-39818
Number of pages4
JournalJournal of Biological Chemistry
Volume275
Issue number51
DOIs
Publication statusPublished - Dec 22 2000
Externally publishedYes

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JNK Mitogen-Activated Protein Kinases
Extracellular Signal-Regulated MAP Kinases
Scaffolds
Chemical activation
Mitogen-Activated Protein Kinases
Proteins
Phosphorylation
COS Cells
Heat-Shock Proteins
Protein Kinases
Acetates

ASJC Scopus subject areas

  • Biochemistry

Cite this

A scaffold protein in the c-Jun NH2-terminal kinase signaling pathways suppresses the extracellular signal-regulated kinase signaling pathways. / Kuboki, Yoshihide; Ito, Michihiko; Takamatsu, Nobuhiko; Yamamoto, Ken-ichi; Shiba, Tadayoshi; Yoshioka, Katsuji.

In: Journal of Biological Chemistry, Vol. 275, No. 51, 22.12.2000, p. 39815-39818.

Research output: Contribution to journalArticle

Kuboki, Yoshihide ; Ito, Michihiko ; Takamatsu, Nobuhiko ; Yamamoto, Ken-ichi ; Shiba, Tadayoshi ; Yoshioka, Katsuji. / A scaffold protein in the c-Jun NH2-terminal kinase signaling pathways suppresses the extracellular signal-regulated kinase signaling pathways. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 51. pp. 39815-39818.
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