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, Junseo
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
C2 - 16716258
AN - SCOPUS:33646825165
VL - 345
SP - 1201
EP - 1206
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -