TY - JOUR
T1 - Molecular cloning of mammalian Spred-3 which suppresses tyrosine kinase-mediated Erk activation
AU - Kato, Reiko
AU - Nonami, Atsushi
AU - Taketomi, Takaharu
AU - Wakioka, Toru
AU - Kuroiwa, Asato
AU - Matsuda, Yoichi
AU - Yoshimura, Akihiko
N1 - Funding Information:
We thank Dr. E. Nishida for the ERK2 plasmid and Dr. T. Sato and Dr. Y. Kaziro for the Ras plasmids. Part of this work was supported by grants from the Ministry of Education, Science, Technology, Sports and Culture of Japan, the Japan Health Science Foundation, the Human Frontier Science Program, the Japan Research Foundation for Clinical Pharmacology, and the Uehara Memorial Foundation.
PY - 2003/3/21
Y1 - 2003/3/21
N2 - 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.
AB - 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.
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U2 - 10.1016/S0006-291X(03)00259-6
DO - 10.1016/S0006-291X(03)00259-6
M3 - Article
C2 - 12646235
AN - SCOPUS:0037459180
SN - 0006-291X
VL - 302
SP - 767
EP - 772
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -