Phosphatidylinositol 3-kinase γ mediates shear stress-dependent activation of JNK in endothelial cells

被引:90
作者
Go, YM
Park, HY
Maland, MC
Darley-Usmar, VM
Stoyanov, B
Wetzker, R
Jo, HJ
机构
[1] Univ Alabama, Dept Pathol, Div Mol & Cellular Pathol, Birmingham, AL 35294 USA
[2] Univ Jena, Max Planck Res Unit Mol Cell Biol, D-07747 Jena, Germany
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 1998年 / 275卷 / 05期
关键词
mechanotransduction; extracellular signal-regulated kinase; G proteins; atherosclerosis;
D O I
10.1152/ajpheart.1998.275.5.H1898
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Shear stress differentially activates extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) by mechanisms involving G alpha(12) and G beta/gamma proteins, respectively, in bovine aortic endothelial cells (BAEC). The early events in this signaling mechanism by which G proteins regulate ERK and JNK in response to shear stress have not been defined. Here we show that BAEC endogenously express a G protein-dependent form of phosphatidylinositol 3-kinase, PI3K gamma, and its activity is stimulated by shear stress. PI3K gamma activity was measured in vitro using BAEC that were transiently transfected with an epitope-tagged PI3K gamma (vsv-PI3K gamma). Exposure of BAEC to sheer stress rapidly and transiently stimulated the activity of vsv-PI3K gamma (maximum by 15 s, with a return to basal after 1-min exposure to 5 dyn/cm(2) shear stress). Activity of vsv-PI3K gamma was stimulated by sheer stress intensities as low as 0.5 dyn/cm(2). Treatment of BAEC with an inhibitor of PI3K, wortmannin, inhibited shear-dependent activation of JNK but had no effect on that of ERK. Furthermore, expression of a kinase-inactive mutant (PI3K gamma(K799R)) in BAEC inhibited the shear-dependent activation of JNK but not ERK. Taken together, these results suggest that PI3K gamma selectively regulates the shear-sensitive JNK pathway. This differential and novel signaling pathway may be responsible for coordinating various mechanosensitive events in endothelial cells.
引用
收藏
页码:H1898 / H1904
页数:7
相关论文
共 43 条
[11]   Differential effect of shear stress on extracellular signal-regulated kinase and N-terminal Jun kinase in endothelial cells - G(i)2- and G beta/gamma-dependent signaling pathways [J].
Jo, H ;
Sipos, K ;
Go, YM ;
Law, R ;
Rong, J ;
McDonald, JM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (02) :1395-1401
[12]   ENDOTHELIAL ALBUMIN PERMEABILITY IS SHEAR DEPENDENT, TIME-DEPENDENT, AND REVERSIBLE [J].
JO, H ;
DULL, RO ;
HOLLIS, TM ;
TARBELL, JM .
AMERICAN JOURNAL OF PHYSIOLOGY, 1991, 260 (06) :H1992-H1996
[13]   SIGNAL-TRANSDUCTION FROM THE CELL-SURFACE TO THE NUCLEUS THROUGH THE PHOSPHORYLATION OF TRANSCRIPTION FACTORS [J].
KARIN, M .
CURRENT OPINION IN CELL BIOLOGY, 1994, 6 (03) :415-424
[14]   NUCLEAR FACTOR-KAPPA-B INTERACTS FUNCTIONALLY WITH THE PLATELET-DERIVED GROWTH-FACTOR B-CHAIN SHEAR-STRESS RESPONSE ELEMENT IN VASCULAR ENDOTHELIAL-CELLS EXPOSED TO FLUID SHEAR-STRESS [J].
KHACHIGIAN, LM ;
RESNICK, N ;
GIMBRONE, MA ;
COLLINS, T .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 96 (02) :1169-1175
[15]   PULSATILE FLOW AND ATHEROSCLEROSIS IN THE HUMAN CAROTID BIFURCATION - POSITIVE CORRELATION BETWEEN PLAQUE LOCATION AND LOW AND OSCILLATING SHEAR-STRESS [J].
KU, DN ;
GIDDENS, DP ;
ZARINS, CK ;
GLAGOV, S .
ARTERIOSCLEROSIS, 1985, 5 (03) :293-302
[16]   ROLE OF G-PROTEINS IN SHEAR STRESS-MEDIATED NITRIC-OXIDE PRODUCTION BY ENDOTHELIAL-CELLS [J].
KUCHAN, MJ ;
JO, H ;
FRANGOS, JA .
AMERICAN JOURNAL OF PHYSIOLOGY, 1994, 267 (03) :C753-C758
[17]   STIMULATION OF TRANSCRIPTION FACTORS NF-KAPPA-B AND AP1 IN ENDOTHELIAL-CELLS SUBJECTED TO SHEAR-STRESS [J].
LAN, QX ;
MERCURIUS, KO ;
DAVIES, PF .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1994, 201 (02) :950-956
[18]   Fluid shear stress activation of focal adhesion kinase - Linking to mitogen-activated protein kinases [J].
Li, S ;
Kim, M ;
Hu, YL ;
Jalali, S ;
Schlaepfer, DD ;
Hunter, T ;
Chien, S ;
Shyy, JYJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (48) :30455-30462
[19]  
Li YS, 1996, MOL CELL BIOL, V16, P5947
[20]   Shear stress induction of the tissue factor gene [J].
Lin, MC ;
AlmusJacobs, F ;
Chen, HH ;
Parry, GCN ;
Mackman, N ;
Shyy, JYJ ;
Chien, S .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 99 (04) :737-744