title: XIAP reverses various functional activities of FRNK in endothelial cells.
abstract: In endothelial cells, focal adhesion kinase (FAK) regulates cell proliferation, migration, adhesion, and shear-stimulated activation of MAPK. We recently found that FAK is recruited into focal adhesion (FA) sites through interactions with XIAP (X-chromosome linked inhibitor of apoptosis protein) and activated by Src kinase in response to shear stress. In this study, we examined which domain(s) of FAK is(are) important for various vascular functions such as FA recruiting, XIAP-binding and shear stress-stimulated ERK activation. Through a series of experiments, we determined that the FRNK domain is recruited into FA sites and promotes endothelial cell adhesion. Interestingly, XIAP knockdown was shown to reduce FA recruitment of FRNK and the cell adhesive effect of FRNK. In addition, we found that XIAP interacts with FRNK, suggesting cross-talk between XIAP and FRNK. We also demonstrated that FRNK inhibits endothelial cell migration and shear-stimulated ERK activation. These inhibitory effects of FRNK were reversed by XIAP knockdown. Taken together, we can conclude that XIAP plays a key role in vascular functions of FRNK or FRNK domain-mediated vascular functions of FAK.
authors.affiliation: Department of Molecular Biology & Institute of Nanosensor and Biotechnology, BK21 Graduate Program for RNA Biology, Dankook Univiersity, 126, Jukjeon-dong, Suji-gu, Yongin-si, Gyeonggi-do 448-701, Republic of Korea.
authors.forename: Sunyoung
authors.initials: S
authors.lastname: Ahn
authors.forename: Hyun Jeong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Sung-Gil
authors.initials: SG
authors.lastname: Chi
authors.forename: Heonyong
authors.initials: H
authors.lastname: Park
mesh_terms: D000818:Animals; D002417:Cattle; D002448:Cell Adhesion; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000378:metabolism*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D013314:Stress, Mechanical; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D051636:X-Linked Inhibitor of Apoptosis Protein; C113183:FAK-related nonkinase; D011505:Protein-Tyrosine Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases