XIAP is essential for shear stress-enhanced Tyr-576 phosphorylation of FAK

Biochemical and Biophysical Research Communications
Sunyoung Ahn, Heonyong Park

Abstract

In endothelial cells, X-chromosome linked inhibitor of apoptosis protein (XIAP) regulates cell survival, migration and adhesion. We have recently found that XIAP recruits focal adhesion kinase (FAK) into integrin-associated focal adhesions, controlling cell migration. However, little is understood about the molecular mechanisms by which FAK modulation is controlled by XIAP. In this study, we show that XIAP modulates FAK activity through the control of FAK phosphorylation. In bovine aortic endothelial cells (BAEC), phosphorylation of Tyr-576 in FAK is elevated by laminar shear stress. This elevated phosphorylation appears to be responsible for shear stress-stimulated ERK activation. We found that XIAP knockdown reduces shear stress-enhanced phosphorylation of Tyr-576 and induces shear stress-triggered translocation of FAK into nucleus. Nuclear translocation of FAK reduces contact between FAK and Src, a kinase which phosphorylates Tyr-576. This spatial segregation of FAK from Src decreases Tyr-576 phosphorylation and thus shear-stimulated ERK activation. Taken together, our results demonstrate that XIAP plays a key role in shear stress-stimulated ERK activation by maintaining the Src-accessible location of FAK.

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Citations

May 21, 2013·Molecules and Cells·Ssang-Taek Steve Lim
Sep 7, 2013·Cell Death & Disease·T K Oberoi-KhanujaK Rajalingam
Sep 12, 2012·Current Opinion in Lipidology·Carlos ZaragozaMarta Saura
Oct 30, 2015·Scandinavian Journal of Gastroenterology·Jakob B Seidelin
Jul 12, 2011·Microvascular Research·Noureddine ZebdaKonstantin G Birukov
Nov 12, 2013·Biochemical and Biophysical Research Communications·Hye-Rim LeeHeonyong Park
Mar 1, 2012·Biochemical and Biophysical Research Communications·Sunyoung AhnHeonyong Park
Mar 15, 2015·Seminars in Cell & Developmental Biology·Laurence Dubrez, Krishnaraj Rajalingam
Jun 13, 2019·Journal of Experimental & Clinical Cancer Research : CR·Jin ZhouLiling Tang
Nov 13, 2014·Journal of Pediatric Endocrinology & Metabolism : JPEM·Ganesh S JevalikarMatthew A Sabin
Feb 23, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Youngsik SeoHeonyong Park
Nov 15, 2014·American Journal of Physiology. Gastrointestinal and Liver Physiology·Jakob Benedict SeidelinOle Haagen Nielsen
Jun 26, 2020·Pharmacology & Therapeutics·Swati KumarRichard C Turkington

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