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The Sprouty‐related protein, Spred‐1, localizes in a lipid raft/caveola and inhibits ERK activation in collaboration with caveolin‐1
Author(s) -
ami Atsushi,
Taketomi Takaharu,
Kimura Akiko,
Saeki Kazuko,
Takaki Hiromi,
Sanada Takahito,
Taniguchi Koji,
Harada Mine,
Kato Reiko,
Yoshimura Akihiko
Publication year - 2005
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2005.00886.x
Subject(s) - mapk/erk pathway , microbiology and biotechnology , biology , lipid raft , phosphorylation , cell growth , signal transduction , biochemistry
Caveolin‐1 (Cav‐1) has been suggested to function as a negative regulator of mitogen‐stimulated proliferation and the Ras‐p42/44 ERK (MAP kinase) pathway in a variety of cell types. However, the molecular basis of this suppression has not been clarified. Spred/Sprouty family proteins are also negative regulators of the ERK pathway by interacting with Raf‐1. The Spred/Sprouty family proteins contain a cysteine‐rich (CR) domain at the C‐terminus, which is thought to be palmitoylated like Cav‐1 and necessary for membrane anchoring. In this study, we demonstrated that Spred‐1 localized in cholesterol‐rich membrane raft/caveola fractions and interacted with Cav‐1. To clarify the biological effect of Cav‐1/Spred‐1 interaction, we used hematopoietic cells that lacked expression of caveolins but expressed Spred‐1. Forced expression of Cav‐1 suppressed SCF‐ and IL‐3‐induced proliferation and ERK activation. Furthermore, forced expression of exogenous Spred‐1 in Cav‐1‐expressing cells further suppressed proliferation and ERK activation. These data suggest that Spred‐1 inhibits ERK activation in collaboration with Cav‐1.