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

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


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
Issue number3
Publication statusPublished - 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.


  • Cell adhesion
  • Cell migration
  • Cell spreading
  • Rap1
  • TIMP-2

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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