MEK5/ERK5 signaling modulates endothelial cell migration and focal contact turnover.
The formation of new blood vessels from pre-existing ones requires highly coordinated restructuring of endothelial cells (EC) and the surrounding extracellular matrix. Directed EC migration is a central step in this process and depends on cellular signaling cascades that initiate and control the structural rearrangements. On the basis of earlier findings that ERK5 deficiency in mouse EC results in massive defects in vessel architecture, we focused on the impact of the MEK5/ERK5 signaling pathway on EC migration. Using a retroviral gene transfer approach, we found that constitutive activation of MEK5/ERK5 signaling strongly inhibits EC migration and results in massive morphological changes. The area covered by spread EC was dramatically enlarged, accompanied by an increase in focal contacts and altered organization of actin filaments. Consequently, cells were more rigid and show reduced motility. This phenotype was most likely based on decreased focal contact turnover caused by reduced expression of p130Cas, a key player in directed cell migration. We demonstrate for the first time that ERK5 signaling not only is involved in EC survival and stress response but also controls migration and morphology of EC.
Spiering
Désirée
D
Institute of Molecular Virology (IMV), Center of Molecular Biology of Inflammation (ZMBE), and Interdisciplinary Center of Medical Research (IZKF), Universitaetsklinikum Muenster, 48149 Muenster, Germany.
Schmolke
Mirco
M
Ohnesorge
Nils
N
Schmidt
Marc
M
Goebeler
Matthias
M
Wegener
Joachim
J
Wixler
Viktor
V
Ludwig
Stephan
S
D002465:Cell Movement; D002470:Cell Survival; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology*; D006801:Humans; D048671:MAP Kinase Kinase 5 / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D048054:Mitogen-Activated Protein Kinase 7 / Q000378:metabolism*; D008954:Models, Biological; D009389:Neovascularization, Pathologic; D010641:Phenotype; D015398:Signal Transduction; D014162:Transfection; D014945:Wound Healing
D048054:Mitogen-Activated Protein Kinase 7; D048671:MAP Kinase Kinase 5