title: JNK2 promotes endothelial cell alignment under flow.
abstract: Endothelial cells in straight, unbranched segments of arteries elongate and align in the direction of flow, a feature which is highly correlated with reduced atherosclerosis in these regions. The mitogen-activated protein kinase c-Jun N-terminal kinase (JNK) is activated by flow and is linked to inflammatory gene expression and apoptosis. We previously showed that JNK activation by flow is mediated by integrins and is observed in cells plated on fibronectin but not on collagen or basement membrane proteins. We now show thatJNK2 activation in response to laminar shear stress is biphasic, with an early peak and a later peak. Activated JNK localizes to focal adhesions at the ends of actin stress fibers, correlates with integrin activation and requires integrin binding to the extracellular matrix. Reducing JNK2 activation by siRNA inhibits alignment in response to shear stress. Cells on collagen, where JNK activity is low, align slowly. These data show that an inflammatory pathway facilitates adaptation to laminar flow, thereby revealing an unexpected connection between adaptation and inflammatory pathways.
authors: Department of Microbiology, University of Virginia, Charlottesville, Virginia, United States of America.
authors: Cornelia
authors: C
authors: Hahn
authors: Chong
authors: C
authors: Wang
authors: A Wayne
authors: AW
authors: Orr
authors: Brian G
authors: BG
authors: Coon
authors: Martin Alexander
authors: MA
authors: Schwartz
mesh_terms: D000818:Animals; D002417:Cattle; D003094:Collagen / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000494:pharmacology; D022001:Focal Adhesions / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D016023:Integrins / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism*; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012212:Rheology / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013314:Stress, Mechanical
chemical_list: D005353:Fibronectins; D016023:Integrins; D051419:Paxillin; D003094:Collagen; D048056:Mitogen-Activated Protein Kinase 9