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, Jun Seo Oh

Research output: Contribution to journalArticle

8 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 languageEnglish
Pages (from-to)1201-1206
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume345
Issue number3
DOIs
Publication statusPublished - 2006 Jul 7

Fingerprint

Tissue Inhibitor of Metalloproteinase-2
Cell Adhesion
Up-Regulation
Adhesion
Endothelial cells
Cell adhesion
Endothelial Cells
Cell Movement
Actins
Paxillin
Phenotype
Guanosine Triphosphate
Actin Cytoskeleton

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 journalArticle

Chang, Hyeujin ; Lee, Jungeun ; Poo, Haryoung ; Noda, Makoto ; Diaz, Terre ; Wei, Beiyang ; Stetler-Stevenson, William G. ; Oh, Jun Seo. / TIMP-2 promotes cell spreading and adhesion via upregulation of Rap1 signaling. In: Biochemical and Biophysical Research Communications. 2006 ; Vol. 345, No. 3. pp. 1201-1206.
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