The p38/mitogen-activated protein (MAP) kinase-activated protein kinase 2 (
MAPKAP kinase 2)/heat shock protein (HSP)25/27 pathway is thought to play a
critical role in actin dynamics. In the present study, we examined whether
p38 was involved in the morphological changes seen in endothelial cells (E
C) exposed to shear stress. Cultured bovine aortic EC were subjected to 14
dyn/cm(2) laminar steady shear stress. Peak activation of p38, MAPKAP kinas
e 2, and HSP25 were sixfold at 5 min, sixfold at 5 min, and threefold at 30
min compared with static control, respectively. SB-203580 (1 muM), a speci
fic inhibitor of p38, abolished the activation of MAPKAP kinase 2 and HSP25
as well as EC elongation and alignment in the direction of flow elicited b
y shear stress. The mean orientation angle of cells subjected to shear with
out SB-203580, with SB-203580, or static control were 17, 50, and 43 degree
s, respectively (P< 0.05). EC transfected with the dominant negative mutant
of p38-<alpha> aligned randomly with no stress fiber formation despite exp
osure to shear stress. These data suggests that the pathway of p38/ MAPKAP
kinase 2/HSP25/27 is activated in response to shear stress, and this pathwa
y plays an important role in morphological changes induced by shear stress.