c-Abl mediates endothelial apoptosis induced by inhibition of integrins alphavbeta3 and alphavbeta5 and by disruption of actin.

Blood
Jingying XuAnat Erdreich-Epstein

Abstract

Inhibition of integrins alphavbeta3 and alphavbeta5 in human brain microvascular endothelial cells (HBMECs) by the function-blocking peptide RGDfV induces loss of spreading on vitronectin, cell detachment, and apoptosis. We demonstrate that cell detachment is not required for apoptosis because plating on bovine serum albumin-blocked poly-L-lysine (allows attachment, but not integrin ligation and cell spreading) also induced apoptosis. Latrunculin B (LatB), which inhibits F-actin polymerization, induced transient loss of HBMEC spreading on vitronectin, but not their detachment, and induced apoptosis despite recovery of cell spreading. However, LatB did not cause apoptosis in 5 tumor cell lines. In HBMECs, both LatB and RGDfV induced transient Y412 and Y245 phosphorylation of endogenous c-Abl, a nonreceptor tyrosine kinase that reciprocally regulates F-actin. LatB also induced nuclear translocation of c-Abl in HBMECs. STI-571 (imatinib), a targeted therapy for BCR-ABL1(+) leukemias and inhibitor of c-Abl, platelet-derived growth factor receptor, and c-Kit, decreased endothelial apoptosis. LatB-induced HBMEC apoptosis, and its inhibition by STI-571 also occurred in a 3-dimensional collagen model, supporting physiologic relevance. ...Continue Reading

References

Apr 22, 1994·Science·P C BrooksD A Cheresh
Jul 15, 1996·The Journal of Clinical Investigation·S StrömbladD A Cheresh
Sep 3, 1996·Proceedings of the National Academy of Sciences of the United States of America·M FriedlanderD A Cheresh
Dec 24, 1996·Proceedings of the National Academy of Sciences of the United States of America·J M LewisJ Y Wang
Feb 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·Z M YuanD Kufe
May 30, 1997·Science·C S ChenD E Ingber
Jun 11, 1998·The Journal of Biological Chemistry·J M Lewis, M A Schwartz
Jun 24, 1998·Proceedings of the National Academy of Sciences of the United States of America·S TaageperaT J Hope
Apr 20, 2001·The Journal of Biological Chemistry·P J WoodringJ Y Wang
Feb 28, 2002·The Journal of Cell Biology·Pamela J WoodringTony Hunter
Oct 22, 2002·The Journal of Biological Chemistry·Anat Erdreich-EpsteinMelissa Millard
Apr 1, 2003·Molecular and Cellular Biology·Daniela BarilàRoberto Testi
May 31, 2003·Journal of Cell Science·Pamela J WoodringJean Y J Wang
Aug 21, 2003·Proceedings of the National Academy of Sciences of the United States of America·Tony TruongMartin Alexander Schwartz
Dec 6, 2003·Cell Death and Differentiation·N MachuyT Rudel
Jul 13, 2004·Biochimica Et Biophysica Acta·Scott D Blystone
Jan 6, 2005·The Journal of Biological Chemistry·Pamela J WoodringJean Y J Wang
Mar 12, 2005·Cellular and Molecular Life Sciences : CMLS·S WiesnerR Fässler
Oct 26, 2005·Biochemical Society Transactions·C W Gourlay, K R Ayscough
Nov 4, 2005·The Journal of Biological Chemistry·Monica HolcombRichard L Klemke
Oct 13, 2006·The Journal of Experimental Medicine·Ganapati H MahabeleshwarTatiana V Byzova
Dec 23, 2006·Current Opinion in Cell Biology·Isabelle Delon, Nicholas H Brown
Apr 18, 2007·Apoptosis : an International Journal on Programmed Cell Death·Stefanie NottrottRalf Gerhard
Aug 19, 2007·Methods in Enzymology·Alireza Alavi, Dwayne G Stupack
Feb 19, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Tobey J MacDonaldLarry E Kun
Feb 22, 2008·Cell Cycle·Ganapati H MahabeleshwarTatiana V Byzova
Jul 2, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Alejandra R AlvarezSilvana Zanlungo
Oct 2, 2008·Journal of Cell Science·Sayan MitraRina Plattner
Oct 22, 2008·Oncogene·D A Cheresh, D G Stupack
Nov 5, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·David A ReardonL Burt Nabors
Dec 3, 2008·Cell Biochemistry and Biophysics·Payaningal R SomanathTatiana V Byzova

❮ Previous
Next ❯

Citations

Mar 22, 2013·Journal of Molecular Histology·Xinghua ChenGuohua Ding
Sep 8, 2012·Journal of Cell Communication and Signaling·Tadashi HonjoTeruko Takano-Yamamoto
Sep 29, 2011·Current Opinion in Oncology·Koen van Besien
Jan 28, 2012·American Journal of Respiratory Cell and Molecular Biology·Hong-Beom BaeEdward Abraham
Mar 30, 2016·Circulation·Joerg HerrmannKonstantinos Marmagkiolis
Jan 10, 2014·American Journal of Physiology. Cell Physiology·R Scott StephensDavid B Pearse
Sep 27, 2019·Scientific Reports·Anup S PathaniaAnat Erdreich-Epstein
Jul 5, 2017·Frontiers in Microbiology·Saehong MinSoon B Hwang
Apr 20, 2012·Molecular Cancer Research : MCR·Lon D RidgwayDario Marchetti

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.