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Title 

TIMP-2 promotes cell spreading and adhesion via upregulation of Rap1 signaling

 

Rap-1조절에 의한 TIMP-2의 세포 부착 유도 연구

Authors 

H ChangJ LeeHaryoung PooM NodaT DiazB WeiW G Stetler-StevensonJ Oh

Publisher 

Elsevier

Issue Date 

2006

Citation 

Biochemical and Biophysical Research Communications, vol. 345, no. 3, pp. 1201-1206

Keywords 

cell adhesioncell migrationcell spreadingRap1TIMP-2Rap1 proteintissue inhibitor of metalloproteinase 2cell structure

Abstract 

We previously demonstrated that TIMP-2 treatment of human microvascular endothelial cells (hMVECs) activates Rap1 via the pathway of paxillin-Crk-C3G. Here, we show that TIMP-2 overexpression in hMVECs by adenoviral infection enhances Rap1 expression, leading to further increase in Rap1-GTP. TIMP-2 expression, previously reported to inhibit cell migration, also leads to cell spreading accompanied with increased cell adhesion. HMVECs stably expressing Rap1 display a similar phenotype as hMVECs-TIMP-2, whereas the expression of inactive Rap1 mutant, Rap1(38N), leads to elongated appearance with greatly reduced cell adhesion. Furthermore, the phenotype of hMVECs-Rap1(38N) was not reversed by TIMP-2 overexpression. TIMP-2 greatly promotes the association of Rap1 with actin. Therefore, these findings suggest that TIMP-2 mediated alteration in cell morphology requires Rap1, TIMP-2 may recruit Rap1 to sites of actin cytoskeleton remodeling necessary for cell spreading, and enhanced cell adhesion by TIMP-2 expression may hinder cell migration.

ISSN 

0006-291X

Link 

http://dx.doi.org/10.1016/j.bbrc.2006.05.044

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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