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Down-regulation of Sprouty2 via p38 MAPK plays a key role in the induction of cellular apoptosis by tumor necrosis factor-alpha.

Abstract：

:Mammalian Sprouty2 (Spry2) is a key regulator of the receptor tyrosine kinase/ERK signaling pathway and involved in many biological processes, including cell growth, migration, and tumor suppression. Here, we demonstrated that the intracellular protein level of Spry2 was significantly down-regulated by tumor necrosis factor-alpha (TNF-alpha) in both murine Swiss 3T3 fibroblasts and MLE15 lung epithelial cells. Although TNF-alpha activates multiple signaling cascades, only the inhibitor of p38 MAPK pathway blocked TNF-alpha-induced Spry2 down-regulation. Moreover, since both the mRNA level and protein half-life of Spry2 were unaltered by TNF-alpha treatment, this indicated the possible involvement of a translational mechanism in mediating the inhibitory effect of TNF-alpha. Importantly, rescue of the TNF-alpha-induced down-regulation of Spry2 by gene overexpression led to reverse of the apoptotic effect of TNF-alpha in Swiss 3T3 cells. To our knowledge, this study is the first that reported the association of Spry2 with TNF-alpha signaling pathway.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Ding W,Warburton D

doi

10.1016/j.bbrc.2008.08.037

subject

Has Abstract

pub_date

2008-10-24 00:00:00

pages

460-4

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(08)01581-7

journal_volume

375

pub_type

杂志文章

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