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.
| Original language | English |
|---|---|
| Pages (from-to) | 1201-1206 |
| Number of pages | 6 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 345 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2006 Jul 7 |
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Keywords
- Cell adhesion
- Cell migration
- Cell spreading
- Rap1
- TIMP-2
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology
Cite this
TIMP-2 promotes cell spreading and adhesion via upregulation of Rap1 signaling. / Chang, Hyeujin; Lee, Jungeun; Poo, Haryoung; Noda, Makoto; Diaz, Terre; Wei, Beiyang; Stetler-Stevenson, William G.; Oh, Jun Seo.
In: Biochemical and Biophysical Research Communications, Vol. 345, No. 3, 07.07.2006, p. 1201-1206.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - TIMP-2 promotes cell spreading and adhesion via upregulation of Rap1 signaling
AU - Chang, Hyeujin
AU - Lee, Jungeun
AU - Poo, Haryoung
AU - Noda, Makoto
AU - Diaz, Terre
AU - Wei, Beiyang
AU - Stetler-Stevenson, William G.
AU - Oh, Jun Seo
PY - 2006/7/7
Y1 - 2006/7/7
N2 - 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.
AB - 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.
KW - Cell adhesion
KW - Cell migration
KW - Cell spreading
KW - Rap1
KW - TIMP-2
UR - http://www.scopus.com/inward/record.url?scp=33646825165&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33646825165&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2006.05.044
DO - 10.1016/j.bbrc.2006.05.044
M3 - Article
VL - 345
SP - 1201
EP - 1206
JO - The BMJ
JF - The BMJ
SN - 0730-6512
IS - 3
ER -