Upregulation of fibronectin expression by COX-2 is mediated by interaction with ELMO1. Cell Signal 2011 Jan;23(1):99-104
Date
08/25/2010Pubmed ID
20732417Pubmed Central ID
PMC2956838DOI
10.1016/j.cellsig.2010.08.008Scopus ID
2-s2.0-77957823927 (requires institutional sign-in at Scopus site) 17 CitationsAbstract
Engulfment and cell motility 1 (ELMO1), a bipartite guanine nucleotide exchange factor (GEF) for the small GTPase Rac 1, was identified as a susceptibility gene for glomerular disease. Here, we reported that ELMO1 interacted with COX-2 in human mesangial cells. Furthermore, we identified ELMO1 as a posttranslational regulator of COX-2 activity. We demonstrated that COX-2 cyclooxygenase activity increased fibronectin promoter activity. The protein-protein interaction between ELMO1 and COX-2 increased the cyclooxygenase activity of COX-2 and, correspondingly, fibronectin expression. We also found that ET625, the dominant negative form of ELMO1 lacking Rac1 activity, interacted with COX-2, increased cyclooxygenase activity of COX-2 and enhanced COX-2-mediated fibronectin upregulation. To further rule out Rac1 as an ELMO1-mediated regulator of COX-2 activity, we employed the constitutive active Rac1, Rac1(Q63E), and demonstrated that Rac1 signaling has no effect on COX-2-mediated fibronectin promoter activity. These results suggest that ELMO1 contributes to the development of glomerular injury through serving as a regulator of COX-2 activity. The interaction of ELMO1 with COX-2 could play an important role in the development and progression of renal glomerular injury.
Author List
Yang C, Sorokin AAuthor
Andrey Sorokin PhD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adaptor Proteins, Signal TransducingCyclooxygenase 2
Fibronectins
Humans
Mesangial Cells
Promoter Regions, Genetic
Protein Binding
Signal Transduction
Up-Regulation
rac1 GTP-Binding Protein
