c-Abl mediated tyrosine phosphorylation of paxillin regulates LPS-induced endothelial dysfunction and lung injury

American Journal of Physiology. Lung Cellular and Molecular Physiology
Panfeng FuViswanathan Natarajan

Abstract

Paxillin is phosphorylated at multiple residues; however, the role of tyrosine phosphorylation of paxillin in endothelial barrier dysfunction and acute lung injury (ALI) remains unclear. We used siRNA and site-specific nonphosphorylable mutants of paxillin to abrogate the function of paxillin to determine its role in lung endothelial permeability and ALI. In vitro, lipopolysaccharide (LPS) challenge of human lung microvascular endothelial cells (HLMVECs) resulted in enhanced tyrosine phosphorylation of paxillin at Y31 and Y118 with no significant change in Y181 and significant barrier dysfunction. Knockdown of paxillin with siRNA attenuated LPS-induced endothelial barrier dysfunction and destabilization of VE-cadherin. LPS-induced paxillin phosphorylation at Y31 and Y118 was mediated by c-Abl tyrosine kinase, but not by Src and focal adhesion kinase. c-Abl siRNA significantly reduced LPS-induced endothelial barrier dysfunction. Transfection of HLMVECs with paxillin Y31F, Y118F, and Y31/118F double mutants mitigated LPS-induced barrier dysfunction and VE-cadherin destabilization. In vivo, the c-Abl inhibitor AG957 attenuated LPS-induced pulmonary permeability in mice. Together, these results suggest that c-Abl mediated tyrosine ...Continue Reading

References

Nov 18, 1997·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·J M Daniel, A B Reynolds
Jun 11, 1998·The Journal of Biological Chemistry·J M Lewis, M A Schwartz
May 4, 2000·The New England Journal of Medicine·L B Ware, M A Matthay
Sep 25, 2001·Journal of Applied Physiology·S M Dudek, J G Garcia
Jan 5, 2002·International Journal of Cancer. Journal International Du Cancer·Teruo IwasakiHitoshi Akedo
Nov 26, 2002·The Journal of Cell Biology·Asako TsubouchiHisataka Sabe
Dec 17, 2002·Journal of Applied Physiology·Yasushi ShikataJoe G N Garcia
Apr 18, 2003·The New England Journal of Medicine·Greg S MartinMarc Moss
Dec 6, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yasushi ShikataJoe G N Garcia
Jan 27, 2004·Nature Cell Biology·Donna J WebbAlan F Horwitz
Apr 27, 2004·The Journal of Biological Chemistry·Cécile VindisUyen Huynh-Do
Aug 17, 2004·The Journal of Biological Chemistry·Ana M VallésBrigitte Boyer
Sep 24, 2004·Physiological Reviews·Michael C Brown, Christopher E Turner
Jul 26, 2005·American Journal of Physiology. Lung Cellular and Molecular Physiology·Peter V Usatyuk, Viswanathan Natarajan
Nov 3, 2006·American Journal of Respiratory Cell and Molecular Biology·George SuJean-François Pittet
Jan 4, 2008·Journal of Molecular Signaling·Danielle M ScheswohlMichael D Schaller
Feb 5, 2008·American Journal of Physiology. Lung Cellular and Molecular Physiology·Anuran ChatterjeeJohn D Catravas
Jul 31, 2008·American Journal of Respiratory Cell and Molecular Biology·Anna A BirukovaKonstantin G Birukov
Aug 5, 2008·American Journal of Physiology. Lung Cellular and Molecular Physiology·Anna A BirukovaKonstantin G Birukov
May 14, 2009·Journal of Cell Science·Alok TomarDavid D Schlaepfer
Jun 6, 2009·Investigative Ophthalmology & Visual Science·Shinichiro TeranishiTeruo Nishida
Jul 12, 2011·American Journal of Physiology. Lung Cellular and Molecular Physiology·Adrián González-LópezGuillermo M Albaiceta
Sep 8, 2011·Journal of Cellular Biochemistry·Galyna KlevetaKatarzyna Kwiatkowska
Jan 24, 2012·Developmental Cell·Xiao Lei ChenDavid D Schlaepfer
Jul 31, 2012·American Journal of Respiratory Cell and Molecular Biology·Eric KratzerAnna A Birukova
Jan 12, 2013·American Journal of Respiratory Cell and Molecular Biology·Panfeng FuViswanathan Natarajan
Sep 21, 2013·Developmental Cell·Monica GiannottaElisabetta Dejana

❮ Previous
Next ❯

Citations

Dec 22, 2015·International Immunopharmacology·Marwa E AbdelmageedGhada M Suddek
Nov 7, 2015·Canadian Journal of Physiology and Pharmacology·Marwa E AbdelmageedGhada M Suddek
Oct 23, 2015·Mediators of Inflammation·Mariana C SouzaMaria G Henriques
Oct 4, 2016·Translational Research : the Journal of Laboratory and Clinical Medicine·Eleftheria LetsiouSteven M Dudek
Jan 9, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Charu RajputDolly Mehta
Jul 3, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·Kaiser M BijliArshad Rahman
May 21, 2017·American Journal of Physiology. Heart and Circulatory Physiology·Patricia ZamoranoFabiola A Sánchez
Dec 17, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·Ting WangStephen M Black
Aug 11, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ameer Ali BohioXueqing Ba
Feb 20, 2017·Journal of Hematology & Oncology·Ana María López-ColoméEdith López
Feb 13, 2021·Cancers·Pinelopi A NikolopoulouVassiliki Kostourou
Aug 18, 2021·Acta Pharmaceutica Sinica. B·Makhloufi ZoulikhaWei He

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

American Journal of Respiratory Cell and Molecular Biology
Yutong ZhaoViswanathan Natarajan
Zhongguo wei zhong bing ji jiu yi xue = Chinese critical care medicine = Zhongguo weizhongbing jijiuyixue
Jian-wen BaiDou-xia Zhang
American Journal of Physiology. Lung Cellular and Molecular Physiology
Anuran ChatterjeeJohn D Catravas
© 2021 Meta ULC. All rights reserved