Molecular cloning of mammalian Spred-3 which suppresses tyrosine kinase-mediated Erk activation

Reiko Kato, Atsushi Nonami, Takaharu Taketomi, Toru Wakioka, Asato Kuroiwa, Yoichi Matsuda, Akihiko Yoshimura

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

We have reported on Spred-1 and Spred-2, which inhibit MAP kinase activation by interacting with c-kit and ras/raf. Here, we report the cloning of a third member in this family, Spred-3. Spred-3 is expressed exclusively in the brain and its gene locates in chromosome 19q13.13 in human. Like Spred-1 and -2, Spred-3 contains an EVH1 domain in the N-terminus and a Sprouty-related cysteine-rich region (SPR domain) in the C-terminus that is necessary for membrane localization. However, Spred-3 does not possess a functional c-kit binding domain (KBD), since the critical amino acid Arg residue in this region was replaced with Gly in Spred-3. Although Spred-3 suppressed growth factor-induced MAP kinase (Erk) activation, inhibitory activity of Spred-3 was lower than that of Spred-1 or Spred-2. By the analysis of chimeric molecules between Spred-3 and Spred-1, we found that the SPR domain, rather than KBD, is responsible for efficient Erk suppression. The finding of Spred-3 revealed the presence of a novel family of regulators for the Ras/MAP kinase pathway, each member of which may have different specificities for extracellular signals.

Original languageEnglish
Pages (from-to)767-772
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume302
Issue number4
DOIs
Publication statusPublished - Mar 21 2003

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Cloning
Molecular Cloning
Protein-Tyrosine Kinases
Phosphotransferases
Chemical activation
Chromosomes
Cysteine
Organism Cloning
Brain
Intercellular Signaling Peptides and Proteins
Genes
Membranes
Amino Acids
Molecules

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Molecular cloning of mammalian Spred-3 which suppresses tyrosine kinase-mediated Erk activation. / Kato, Reiko; Nonami, Atsushi; Taketomi, Takaharu; Wakioka, Toru; Kuroiwa, Asato; Matsuda, Yoichi; Yoshimura, Akihiko.

In: Biochemical and Biophysical Research Communications, Vol. 302, No. 4, 21.03.2003, p. 767-772.

Research output: Contribution to journalArticle

Kato, Reiko ; Nonami, Atsushi ; Taketomi, Takaharu ; Wakioka, Toru ; Kuroiwa, Asato ; Matsuda, Yoichi ; Yoshimura, Akihiko. / Molecular cloning of mammalian Spred-3 which suppresses tyrosine kinase-mediated Erk activation. In: Biochemical and Biophysical Research Communications. 2003 ; Vol. 302, No. 4. pp. 767-772.
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