Exp Mol Med.  2001 Dec;33(4):276-283.

c-Jun N-terminal kinase is involved in motility of endothelial cell

• Shin EY
• Kim SY
• Kim EG

Abstract

Cell motility is essential for a wide range of cellular activities including anigogenesis as well as metastasis of tumor cells. Ras has been implicated in cell migration and invasion, and functions at upstream of mitogen-activated protein kinase (MAPK) families, which include extracellular-signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 MAPK. In the present study, we examined the role of JNK in endothelial cell motility using stable transfectant (DAR-ECV) of ECV304 endothelial cells expressing previously established oncogenic H-Ras (leu 61). DAR-ECV cells showed an enhanced angiogenic potential and motility (approximately 2-fold) compared to ECV304 cells. Western blot analysis revealed constitutive activation of JNK in DAR-ECV cells. Pretreatment of JNK specific inhibitors, curcumin and all trans-retinoic acid, decreased the basal motility of DAR-ECV cells in a dose-dependent manner. These inhibitors also suppressed the motility stimulated by known JNK agonists such as TNFalpha and anisomycin. To further confirm the role of JNK, ECV304 cells expressing dominant active SEK1 (DAS-ECV) were generated. Basal non-stimulated levels of the cellular migration were greater in DAS-ECV clones than those in control ECV304 cells. These results suggest that Ras-SEK1-JNK pathway regulates motility of endothelial cells during angiogenesis.

Keyword

Endothelial cell; Motility; Angiogenesis; Ras; JNK

MeSH Terms

Anisomycin/pharmacology
Cell Line
*Cell Movement
Curcumin/pharmacology
Endothelium, Vascular/cytology/*physiology
Enzyme Activation
Enzyme Inhibitors/pharmacology
Extracellular Matrix/metabolism
Genes, ras/genetics
Human
Matrix Metalloproteinases/physiology
Mitogen-Activated Protein Kinases/*metabolism
Neovascularization, Physiologic
Support, Non-U.S. Gov't
Tretinoin/pharmacology
Tumor Necrosis Factor/pharmacology
Umbilical Veins/cytology
Urinary Plasminogen Activator/physiology