TIMP-2 upregulates RECK expression via dephosphorylation of paxillin tyrosine residues 31 and 118

Jun Seo Oh, T. Diaz, B. Wei, H. Chang, M. Noda, W. G. Stetler-Stevenson

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

We previously demonstrated that TIMP-2 increases the association of Crk with C3G and via subsequent activation of Rap1 enhances the expression of RECK, a membrane-anchored MMP inhibitor. In the present study, we investigate the mechanism of how the TIMP-2 signal is transduced from the α3β1 integrin receptor to the Crk-C3G-Rap1 molecular complex. TIMP-2 treatment of human microvascular endothelial cells (hMVECs) increased the phosphorylation levels of Src at Tyr-527, the negative regulatory site, through enhanced association of Src with Csk. This results in the reduction of Src kinase activity and dephosphorylation of paxillin at Tyr-31/118, the target sites for Src kinase phosphorylation and also the binding sites for the downstream effector Crk. Such TIMP-2 effects accompany the disassembly of paxillin-Crk-DOCK180 molecular complex and, in turn, Rac1 inactivation. On the contrary, levels of paxillin-Crk-C3G complex formation are not reduced, rather slightly increased, which is consistent with our previous finding. Therefore, TIMP-2-mediated inhibition of Src kinase activity leads to the signaling switch from Rac1 to Rap1, thereby leading to enhanced RECK expression.

Original languageEnglish
Pages (from-to)4230-4234
Number of pages5
JournalOncogene
Volume25
Issue number30
DOIs
Publication statusPublished - 2006 Jul 13

Fingerprint

Paxillin
Tissue Inhibitor of Metalloproteinase-2
Tyrosine
Up-Regulation
src-Family Kinases
Phosphorylation
Matrix Metalloproteinase Inhibitors
Integrins
Endothelial Cells
Binding Sites
Membranes

Keywords

  • Paxillin
  • Rac1
  • RECK
  • Src
  • TIMP-2

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

TIMP-2 upregulates RECK expression via dephosphorylation of paxillin tyrosine residues 31 and 118. / Oh, Jun Seo; Diaz, T.; Wei, B.; Chang, H.; Noda, M.; Stetler-Stevenson, W. G.

In: Oncogene, Vol. 25, No. 30, 13.07.2006, p. 4230-4234.

Research output: Contribution to journalArticle

Oh, JS, Diaz, T, Wei, B, Chang, H, Noda, M & Stetler-Stevenson, WG 2006, 'TIMP-2 upregulates RECK expression via dephosphorylation of paxillin tyrosine residues 31 and 118', Oncogene, vol. 25, no. 30, pp. 4230-4234. https://doi.org/10.1038/sj.onc.1209444
Oh, Jun Seo ; Diaz, T. ; Wei, B. ; Chang, H. ; Noda, M. ; Stetler-Stevenson, W. G. / TIMP-2 upregulates RECK expression via dephosphorylation of paxillin tyrosine residues 31 and 118. In: Oncogene. 2006 ; Vol. 25, No. 30. pp. 4230-4234.
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AU - Stetler-Stevenson, W. G.

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