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 journalArticlepeer-review

72 Citations (Scopus)


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
Issue number4
Publication statusPublished - 2003 Mar 21
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Molecular cloning of mammalian Spred-3 which suppresses tyrosine kinase-mediated Erk activation'. Together they form a unique fingerprint.

Cite this