Journal
JOURNAL OF CELLULAR PHYSIOLOGY
Volume 211, Issue 3, Pages 608-617Publisher
WILEY-LISS
DOI: 10.1002/jcp.20966
Keywords
-
Categories
Funding
- NHLBI NIH HHS [HL075349, HL076259] Funding Source: Medline
Ask authors/readers for more resources
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 PPIX in OxPAPC-induced Rac activation, cytoskeletal remodeling, and barrier protective responses in the human pulmonary endothelial cells (EC). OxPAPC induced membrane translocation of Tiam1, beta PIX, Cdc42, and Rac, but did not affect intracellular distribution of Rho and Rho-specific GEF p115-RhoGEF. Protein depletion of Tiam1 and P beta PIX using siRNA approach abolished OxPAPC-induced activation of Rac and its effector PAK 1. EC transfection with Tiam1 -, beta PIX-, 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 beta PIX mediate OxPAPC-induced Rac activation, cytoskeletal remodeling, and barrier protective response in pulmonary endothelium.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available