The Sprouty-related protein, Spred-1, localizes in a lipid raft/caveola and inhibits ERK activation in collaboration with caveolin-1

Atsushi Nonami, Takaharu Taketomi, Akiko Kimura, Kazuko Saeki, Hiromi Takaki, Takahito Sanada, Koji Taniguchi, Mine Harada, Reiko Kato, Akihiko Yoshimura

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)887-895
Number of pages9
JournalGenes to Cells
Volume10
Issue number9
DOIs
Publication statusPublished - Sep 1 2005

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Caveolin 1
Caveolae
Lipids
Proteins
Caveolins
Membranes
MAP Kinase Signaling System
Interleukin-3
Extracellular Signal-Regulated MAP Kinases
Mitogens
Cysteine
Cholesterol

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cell Biology

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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. / Nonami, Atsushi; Taketomi, Takaharu; Kimura, Akiko; Saeki, Kazuko; Takaki, Hiromi; Sanada, Takahito; Taniguchi, Koji; Harada, Mine; Kato, Reiko; Yoshimura, Akihiko.

In: Genes to Cells, Vol. 10, No. 9, 01.09.2005, p. 887-895.

Research output: Contribution to journalArticle

Nonami, A, Taketomi, T, Kimura, A, Saeki, K, Takaki, H, Sanada, T, Taniguchi, K, Harada, M, Kato, R & Yoshimura, A 2005, 'The Sprouty-related protein, Spred-1, localizes in a lipid raft/caveola and inhibits ERK activation in collaboration with caveolin-1', Genes to Cells, vol. 10, no. 9, pp. 887-895. https://doi.org/10.1111/j.1365-2443.2005.00886.x
Nonami, Atsushi ; Taketomi, Takaharu ; Kimura, Akiko ; Saeki, Kazuko ; Takaki, Hiromi ; Sanada, Takahito ; Taniguchi, Koji ; Harada, Mine ; Kato, Reiko ; Yoshimura, Akihiko. / The Sprouty-related protein, Spred-1, localizes in a lipid raft/caveola and inhibits ERK activation in collaboration with caveolin-1. In: Genes to Cells. 2005 ; Vol. 10, No. 9. pp. 887-895.
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