Ectodomain shedding of TGF-alpha and other transmembrane proteins is induced by receptor tyrosine kinase activation and MAP kinase signaling cascades
摘要：
A variety of transmembrane proteins, such as transforming growth factor-alpha (TGF-alpha), tumor necrosis factor-alpha (TNF-alpha) and L-selectin, undergo shedding, i.e. cleavage of the ectodomain, resulting in release of a soluble protein. Although the physiological relevance of ectodomain shedding is well recognized, little is known about the signaling mechanisms activating this process. We show that growth factor activation of cell surface tyrosine kinase receptors induces ectodomain cleavage of transmembrane TGF-alpha through activation of the Erk MAP kinase signaling cascade without the need for new protein synthesis. In addition, expression of constitutively activated MEK1 or its downstream target Erk2 MAP kinase was sufficient to stimulate TGF-alpha shedding. The basal cleavage level in the absence of exogenous growth factor stimulation was due to p38 MAP kinase signaling. Accordingly, a constitutively activated MKK6, a p38 activator, activated TGF-alpha shedding in the absence of exogenous stimuli. In addition to TGF-alpha shedding, these mechanisms also mediate L-selectin and TNF-alpha cleavage. Thus, L-selectin shedding by neutrophils, induced by N-formylmethionyl-leucyl-phenylalanine, was strongly inhibited by inhibitors of Erk MAP kinase or p38 MAP kinase signaling. Our results indicate that activation of Erk and p38 signaling pathways may represent a general physiological mechanism to induce shedding of a variety of transmembrane proteins.
展开
关键词：
ectodomain shedding MAP kinase L-selectin transforming growth factor-<IMG alt=[alpha] src="http://onlinelibrarystatic.wiley.com/undisplayable_characters/0003b1.gif tumor necrosis factor-<IMG alt=[alpha] src="http://onlinelibrarystatic.wiley.com/undisplayable_characters/0003b1.gif
DOI：
10.1093/emboj/18.24.6962
被引量：
年份：
1999
Nature
国家科技图书文献中心
(权威机构)
EBSCO
Wiley
万方医学
查看更多
dx.doi.org
www.ingentaconnect.com
NCBI
Europe PMC
Europe PMC
(全网免费下载)
NCBI
Pubmed Central
(全网免费下载)
AACR
JBC
ResearchGate
ProQuest
ResearchGate
(全网免费下载)
EBSCO
EBSCO
hw-f5-embojnl.highwire.org
embojnl.embopress.org
(全网免费下载)
mendeley.com
jleukbio.org
jpet.aspetjournals.org
fasebj.org
jasn.asnjournals.org
jcb.rupress.org
biochemj.org
jimmunol.org
genesdev.cshlp.org
jcs.biologists.org
molbiolcell.org
cghjournal.org
mysciencework.com
ajpcell.physiology.org
emboj.embopress.org
onAcademic
core.ac.uk
jacionline.org
通过文献互助平台发起求助，成功后即可免费获取论文全文。
相似文献
参考文献
引证文献
来源期刊
引用走势
站内活动
辅助模式
引用
文献可以批量引用啦~
欢迎点我试用！
