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Tiam1 and βPIX mediate Rac‐dependent endothelial barrier protective response to oxidized phospholipids
Author(s) -
Birukova Anna A.,
Malyukova Irina,
Mikaelyan Arsen,
Fu Panfeng,
Birukov Konstantin G.
Publication year - 2007
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20966
Subject(s) - guanine nucleotide exchange factor , microbiology and biotechnology , cdc42 , rac gtp binding proteins , gtpase , cytoskeleton , chemistry , rac1 , gtpase activating protein , intracellular , actin cytoskeleton , biology , signal transduction , cell , g protein , biochemistry
Oxidized 1‐palmitoyl‐2‐arachidonoyl‐ sn ‐glycero‐3‐phosphorylcholine (OxPAPC) exhibits potent barrier protective effects on pulmonary endothelium, which are mediated by small GTPases Rac and Cdc42. However, upstream mechanisms of OxPAPC‐induced small GTPase activation are not known. We studied involvement of Rac/Cdc42‐specific guanine nucleotide exchange factors (GEFs) Tiam1 and βPIX in OxPAPC‐induced Rac activation, cytoskeletal remodeling, and barrier protective responses in the human pulmonary endothelial cells (EC). OxPAPC induced membrane translocation of Tiam1, βPIX, Cdc42, and Rac, but did not affect intracellular distribution of Rho and Rho‐specific GEF p115‐RhoGEF. Protein depletion of Tiam1 and βPIX using siRNA approach abolished OxPAPC‐induced activation of Rac and its effector PAK1. EC transfection with Tiam1‐, βPIX‐, or PAK1‐specific siRNA dramatically attenuated OxPAPC‐induced barrier enhancement, peripheral actin cytoskeletal enhancement, and translocation of actin‐binding proteins cortactin and Arp3. These results show for the first time that Tiam1 and βPIX mediate OxPAPC‐induced Rac activation, cytoskeletal remodeling, and barrier protective response in pulmonary endothelium. J. Cell. Physiol. 211: 608–617, 2007. © 2007 Wiley‐Liss, Inc.