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dc.contributor.authorLu, Z. X.zh_CN
dc.contributor.authorMurray, J. T.zh_CN
dc.contributor.authorLuo, W. J.zh_CN
dc.contributor.authorLi, H. L.zh_CN
dc.contributor.authorWu, X. P.zh_CN
dc.contributor.authorXu, H. X.zh_CN
dc.contributor.authorBacker, J. M.zh_CN
dc.contributor.authorChen, Y. G.zh_CN
dc.contributor.author吕忠显zh_CN
dc.date.accessioned2013-12-12T02:25:38Z
dc.date.available2013-12-12T02:25:38Z
dc.date.issued2002zh_CN
dc.identifier.citationJournal of Biological Chemistry,277(33):29363-29368zh_CN
dc.identifier.issn0021-9258zh_CN
dc.identifier.otherISI:000177509300004zh_CN
dc.identifier.urihttps://dspace.xmu.edu.cn/handle/2288/65983
dc.description.abstractLike many other cell surface receptors, transforming growth factor beta (TGF-beta) receptors are internalized upon ligand stimulation. Given that the signaling-facilitating molecules Smad anchor for receptor activation (SARA) and Hrs are mainly localized in early endosomes, it was unclear whether receptor internalization is required for Smad2 activation. Using reversible biotin labeling, we directly monitored internalization of the TGF-beta type I receptor. Our data indicate that TGF-beta type I receptor is endocytosed via a clathrin-dependent mechanism and is effectively blocked by depletion of intracellular potassium or by expression of a mutant dynamin (K44A). However, blockage of receptor endocytosis by these two means has no effect on TGF-beta-mediated Smad2 activation. Furthermore, TGF-beta-induced Smad2 activation was unaffected by inhibition of hVPS34 activity with wortmannin or inhibitory anti-hVPS34 antibodies. Finally, we demonstrated that Smad2 interacted with cell surface receptors and that a SARA binding-deficient Smad2 mutant was phosphorylated by the receptors. Thus, our findings suggest that receptor endocytosis is dispersible for TGF-beta-mediated activation of Smad2 and that this activation can be mediated by both SARA-dependent and -independent mechanisms.zh_CN
dc.language.isoen_USzh_CN
dc.subjectCLATHRIN-MEDIATED ENDOCYTOSISzh_CN
dc.subjectFYVE DOMAIN PROTEINzh_CN
dc.subjectSIGNAL-TRANSDUCTIONzh_CN
dc.subjectDISTINCT ROLESzh_CN
dc.subjectI RECEPTORzh_CN
dc.subjectDYNAMINzh_CN
dc.subjectINTERNALIZATIONzh_CN
dc.subjectDEGRADATIONzh_CN
dc.subjectTRAFFICKINGzh_CN
dc.subjectPATHWAYzh_CN
dc.titleTransforming growth factor beta activates Smad2 in the absence of receptor endocytosiszh_CN
dc.typeArticlezh_CN


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