TIMP-2 disrupts FGF-2-induced downstream signaling pathways.

Microvascular Research
Dong-Wan SeoW G Stetler-Stevenson

Abstract

We have previously reported that tissue inhibitor of metalloproteinases-2 (TIMP-2), an endogenous inhibitor of matrix metalloproteinase, modulates angiogenic responses through the MMP inhibition-independent activity. In this study, we investigate the molecular mechanisms of TIMP-2-mediated growth inhibition in response to fibroblast growth factor-2 (FGF-2). Pre-treatment with a protein tyrosine phosphatase inhibitor orthovanadate or expression of a dominant negative Shp-1 mutant fails to induce TIMP-2 inactivation of FGF-2 signaling pathways in human microvascular endothelial cells. We also show that TIMP-2 inhibition of FGF-2-induced p42/44(MAPK) activation and cell proliferation is associated with TIMP-2 binding to integrin alpha3beta1 on endothelial cell surfaces, as demonstrated by use of anti-integrin alpha3 or beta1 blocking antibodies, or disruption of integrin alpha3 expression by siRNA. Collectively, our results indicate that TIMP-2 inhibits FGF-2 signaling pathways through association with integrin alpha3beta1 and Shp-1-dependent inhibition of p42/44(MAPK) signaling, which in turn, results in suppression of FGF-2-stimulated endothelial cell mitogenesis.

References

Jun 2, 1995·The Journal of Biological Chemistry·M L Corcoran, W G Stetler-Stevenson
Dec 3, 1998·The Journal of Clinical Investigation·L GuedezM Stetler-Stevenson
May 4, 1999·The Journal of Clinical Investigation·W G Stetler-Stevenson
Jan 27, 2000·Cell·D Hanahan, R A Weinberg
Nov 1, 2000·Cell·J Schlessinger
Jun 8, 2001·Annual Review of Biochemistry·S G Rhee
Mar 30, 2002·Science·Lisa M CoussensLynn M Matrisian
Apr 25, 2002·Molecular and Cellular Biology·Amardeep S DhillonWalter Kolch
Sep 18, 2002·Journal of Cell Science·Andrew H BakerGillian Murphy
Jul 17, 2003·Science's STKE : Signal Transduction Knowledge Environment·Joseph Schlessinger, Mark A Lemmon
Jul 31, 2003·Cell·Dong-Wan SeoWilliam G Stetler-Stevenson
Nov 27, 2004·Trends in Cell Biology·Charles ffrench-Constant, Holly Colognato
Mar 12, 2005·Trends in Molecular Medicine·William G Stetler-Stevenson, Dong-Wan Seo
May 19, 2005·Cancer Research·Pia NybergRaghu Kalluri
May 20, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Leonor Pérez-Martínez, Diane M Jaworski
Dec 6, 2005·The Journal of Biological Chemistry·Dong-Wan SeoWilliam G Stetler-Stevenson
Dec 16, 2005·Nature·Peter Carmeliet
Dec 16, 2005·Nature·Napoleone Ferrara, Robert S Kerbel
Jan 18, 2006·Annual Review of Medicine·Judah Folkman
Mar 25, 2006·Nature Reviews. Cancer·Arne OstmanFrank D Böhmer
May 24, 2006·Biochemical and Biophysical Research Communications·Hyeujin ChangJunseo Oh

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Citations

Apr 22, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Craig S MooreStephen J Crocker
Jul 31, 2010·Journal of Oncology·N E CampbellJ Petrik
Jul 26, 2014·Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology·Janet M C NguPaul W M Fedak
Jul 12, 2011·Cellular and Molecular Life Sciences : CMLS·Hui HuaYangfu Jiang
Jul 16, 2015·Transplant International : Official Journal of the European Society for Organ Transplantation·Timothy J PiantaZoltan H Endre
Dec 4, 2010·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Neetha SantoshFengyu Song
Jul 20, 2010·The American Journal of Pathology·Rita Graça da SilvaKairbaan M Hodivala-Dilke
Dec 10, 2016·Nature Reviews. Cancer·Hartland W JacksonRama Khokha
Jan 24, 2012·Pharmaceuticals·Chandra Shekhar Boosani, Yakkanti A Sudhakar
Jan 20, 2010·Laboratory Investigation; a Journal of Technical Methods and Pathology·Seo-Jin LeeWilliam George Stetler-Stevenson
Aug 6, 2014·Clinical Journal of the American Society of Nephrology : CJASN·Joseph L Alge, John M Arthur
Jun 7, 2019·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Roopali RoyMarsha A Moses
Oct 18, 2019·Carcinogenesis·David PeeneyWilliam G Stetler-Stevenson
Jan 5, 2022·Open Biology·Carolyn G Chen, Renato V Iozzo

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