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

Hyeujin Chang; Jungeun Lee; Haryoung Poo; Makoto Noda; Terre Diaz; Beiyang Wei; William G. Stetler-Stevenson; Junseo Oh

doi:10.1016/j.bbrc.2006.05.044

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

Hyeujin Chang, Jungeun Lee, Haryoung Poo, Makoto Noda, Terre Diaz, Beiyang Wei, William G. Stetler-Stevenson, Junseo Oh

Department of Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

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	https://doi.org/10.1016/j.bbrc.2006.05.044
Publication status	Published - 2006 Jul 7

Bibliographical note

Funding Information:
This work was supported by intramural research funds from the National Cancer Institute, Center for Cancer Research (Project # Z01SC 009179) and by grant from BAERI (M2-0508-02-0000-05-B08-02-000-00) of National Nuclear R&D Program from Ministry of Science and Technology of Korea.

Keywords

Cell adhesion
Cell migration
Cell spreading
Rap1
TIMP-2

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2006.05.044

Cite this

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title = "TIMP-2 promotes cell spreading and adhesion via upregulation of Rap1 signaling",

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.",

keywords = "Cell adhesion, Cell migration, Cell spreading, Rap1, TIMP-2",

author = "Hyeujin Chang and Jungeun Lee and Haryoung Poo and Makoto Noda and Terre Diaz and Beiyang Wei and Stetler-Stevenson, {William G.} and Junseo Oh",

note = "Funding Information: This work was supported by intramural research funds from the National Cancer Institute, Center for Cancer Research (Project # Z01SC 009179) and by grant from BAERI (M2-0508-02-0000-05-B08-02-000-00) of National Nuclear R&D Program from Ministry of Science and Technology of Korea.",

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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

N1 - Funding Information: This work was supported by intramural research funds from the National Cancer Institute, Center for Cancer Research (Project # Z01SC 009179) and by grant from BAERI (M2-0508-02-0000-05-B08-02-000-00) of National Nuclear R&D Program from Ministry of Science and Technology of Korea.

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.

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KW - Cell migration

KW - Cell spreading

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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