Contact inhibition of VEGF-induced proliferation requires vascular endothelial cadherin, beta-catenin, and the phosphatase DEP-1/CD148

The Journal of Cell Biology
Maria Grazia LampugnaniElisabetta Dejana

Abstract

Confluent endothelial cells respond poorly to the proliferative signals of VEGF. Comparing isogenic endothelial cells differing for vascular endothelial cadherin (VE-cadherin) expression only, we found that the presence of this protein attenuates VEGF-induced VEGF receptor (VEGFR) 2 phosphorylation in tyrosine, p44/p42 MAP kinase phosphorylation, and cell proliferation. VE-cadherin truncated in beta-catenin but not p120 binding domain is unable to associate with VEGFR-2 and to induce its inactivation. beta-Catenin-null endothelial cells are not contact inhibited by VE-cadherin and are still responsive to VEGF, indicating that this protein is required to restrain growth factor signaling. A dominant-negative mutant of high cell density-enhanced PTP 1 (DEP-1)//CD148 as well as reduction of its expression by RNA interference partially restore VEGFR-2 phosphorylation and MAP kinase activation. Overall the data indicate that VE-cadherin-beta-catenin complex participates in contact inhibition of VEGF signaling. Upon stimulation with VEGF, VEGFR-2 associates with the complex and concentrates at cell-cell contacts, where it may be inactivated by junctional phosphatases such as DEP-1. In sparse cells or in VE-cadherin-null cells, this ph...Continue Reading

References

Sep 1, 1992·The Journal of Cell Biology·M G LampugnaniE Dejana
Jan 1, 1992·American Journal of Respiratory Cell and Molecular Biology·P A D'Amore
Aug 1, 1995·The Journal of Cell Biology·S M Brady-KalnayN K Tonks
Oct 11, 1994·Proceedings of the National Academy of Sciences of the United States of America·A OstmanN K Tonks
Jul 12, 1996·The Journal of Biological Chemistry·M FuchsA Ullrich
Aug 15, 1996·The Journal of Clinical Investigation·L CavedaE Dejana
Dec 15, 1996·Developmental Biology·F Fagotto, B M Gumbiner
Apr 21, 1999·Current Opinion in Cell Biology·M A Schwartz, V Baron
Aug 18, 1999·Proceedings of the National Academy of Sciences of the United States of America·M CoradaE Dejana
Sep 24, 1999·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·N Ferrara
Oct 3, 1999·Journal of the American Society of Nephrology : JASN·T TakahashiT O Daniel
Dec 2, 1999·Nature Medicine·N Ferrara, K Alitalo
Feb 22, 2000·The Journal of Biological Chemistry·J A UkropecM J Woolkalis
Sep 23, 2000·Nature·P Carmeliet, R K Jain
Feb 13, 2001·Developmental Biology·Y Y KisanukiM Yanagisawa
Mar 15, 2001·Current Opinion in Cell Biology·N K Tonks, B G Neel
Oct 10, 2001·Current Biology : CB·C J Gottardi, B M Gumbiner
Oct 30, 2001·The Journal of Biological Chemistry·K N MeadowsK Pumiglia
Apr 16, 2002·Molecular Biology of the Cell·Maria Grazia LampugnaniElisabetta Dejana
May 2, 2002·Cell·Marc van de WeteringHans Clevers
Jun 25, 2002·Proceedings of the National Academy of Sciences of the United States of America·Ayelet Shay-SalitNitzan Resnick

❮ Previous
Next ❯

Citations

Feb 9, 2006·Cellular and Molecular Life Sciences : CMLS·S Cébe-SuarezK Ballmer-Hofer
Apr 13, 2007·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Robert W McLachlan, Alpha S Yap
Apr 2, 2009·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Masahiro Murakami, Michael Simons
Nov 1, 2011·Functional & Integrative Genomics·Mahesh ThirunavukkarasuNilanjana Maulik
Jun 25, 2004·The American Journal of Pathology·Monica IurlaroElisabetta Dejana
Sep 24, 2005·Nature·Sara M Weis, David A Cheresh
Mar 25, 2006·Nature Reviews. Cancer·Arne OstmanFrank D Böhmer
Dec 24, 2010·Nature Reviews. Cancer·Sofi G JulienMichel L Tremblay
May 25, 2012·Nature Reviews. Cancer·Jessica B Casaletto, Andrea I McClatchey
Feb 25, 2011·Nature Reviews. Molecular Cell Biology·Ugo Cavallaro, Elisabetta Dejana
Jun 17, 2009·Journal de la Société de biologie·Philippe Huber
Jun 25, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jin-Hong KimAnand R Asthagiri
Feb 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Keiko TakahashiTakamune Takahashi
May 6, 2011·The Journal of Biological Chemistry·Ondrej StepanekTomas Brdicka
Jan 26, 2011·The Journal of Biological Chemistry·Deepika AroraJörg P Müller
May 22, 2007·Antioxidants & Redox Signaling·Masuko Ushio-Fukai
Nov 13, 2008·Antioxidants & Redox Signaling·Masuko Ushio-Fukai
Mar 25, 2009·Antioxidants & Redox Signaling·Masuko Ushio-Fukai, Norifumi Urao
Aug 27, 2005·Molecular Biology of the Cell·Kanyan XiaoAndrew P Kowalczyk
Jan 13, 2010·Cold Spring Harbor Perspectives in Biology·Pierre D McCreaMaria S Balda
Jan 13, 2010·Cold Spring Harbor Perspectives in Biology·Ewa StepniakValeri Vasioukhin
Mar 6, 2004·Science·W James Nelson, Roel Nusse
Aug 1, 2008·Journal of Virology·Mandana MansouriKlaus Früh
Oct 22, 2008·Molecular and Cellular Biology·Catherine ChabotIsabelle Royal
Jan 22, 2005·Circulation Research·Nathalie LambengPhilippe Huber
Nov 2, 2013·The Journal of Clinical Investigation·Lei NieMehran M Sadeghi
Apr 19, 2012·Blood·Lucia NapioneFederico Bussolino
Oct 19, 2010·BMC Systems Biology·Chen-Ching LinHsuan-Cheng Huang
May 17, 2011·Vascular Cell·Peter C RaeJustin C St John
Jul 27, 2012·Journal of Cell Science·Masataka SaitoAndrew P Kowalczyk

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
transgenics
Immunoprecipitation
nuclear translocation

Software Mentioned

Excel
Canvas
NIH Image
Adobe Photoshop

Related Concepts

Related Feeds

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.