PMID- 8995450
OWN - NLM
STAT- MEDLINE
DCOM- 19970212
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 272
IP  - 2
DP  - 1997 Jan 10
TI  - Differential effect of shear stress on extracellular signal-regulated kinase and 
      N-terminal Jun kinase in endothelial cells. Gi2- and Gbeta/gamma-dependent 
      signaling pathways.
PG  - 1395-401
AB  - Shear stress differentially regulates production of many vasoactive factors at 
      the level of gene expression in endothelial cells that may be mediated by 
      mitogen-activated protein kinases, including extracellular signal-regulated 
      kinase (ERK) and N-terminal Jun kinase (JNK). Here we show, using bovine aortic 
      endothelial cells (BAEC), that shear stress differentially regulates ERK and JNK 
      by mechanisms involving Gi2 and pertussis toxin (PTx)-insensitive 
      G-protein-dependent pathways, respectively. Shear activated ERK with a rapid, 
      biphasic time course (maximum by 5 min and basal by 30-min shear exposure) and 
      force dependence (minimum and maximum at 1 and 10 dyn/cm2 shear stress, 
      respectively). PTx treatment prevented shear-dependent activation of ERK1/2, 
      consistent with a Gi-dependent mechanism. In contrast, JNK activity was maximally 
      turned on by a threshold level of shear force (0.5 dyn/cm2 or higher) with a much 
      slower and prolonged time course (requiring at least 30 min to 4 h) than that of 
      ERK. Also, PTx had no effect on shear-dependent activation of JNK. To further 
      define the shear-sensitive ERK and JNK pathways, vectors expressing hemagglutinin 
      epitope-tagged ERK (HA-ERK) or HA-JNK were co-transfected with other vectors by 
      using adenovirus-polylysine in BAEC. Expression of the mutant (alpha)i2(G203), 
      antisense G(alpha)i2 and a dominant negative Ras (N17Ras) prevented 
      shear-dependent activation of HA-ERK, while that of (alpha)i2(G204) and antisense 
      (alpha)i3 did not. Expression of a Gbeta/gamma scavenger, the carboxyl terminus 
      of beta-adrenergic receptor kinase (betaARK-ct), and N17Ras inhibited 
      shear-dependent activation of HA-JNK. Treatment of BAEC with genistein prevented 
      shear-dependent activation of ERK and JNK, indicating the essential role of 
      tyrosine kinase(s) in both ERK and JNK pathways. These results provide evidence 
      that 1) Gi2-protein, Ras, and tyrosine kinase(s) are upstream regulators of 
      shear-dependent activation of ERK and 2) that shear-dependent activation of JNK 
      is regulated by mechanisms involving Gbeta/gamma, Ras, and tyrosine kinase(s).
FAU - Jo, H
AU  - Jo H
AD  - Department of Pathology, University of Alabama at Birmingham, 35294, USA. 
      Jo@path.vh.uab.edu
FAU - Sipos, K
AU  - Sipos K
FAU - Go, Y M
AU  - Go YM
FAU - Law, R
AU  - Law R
FAU - Rong, J
AU  - Rong J
FAU - McDonald, J M
AU  - McDonald JM
LA  - eng
GR  - HL53601/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Isoflavones)
RN  - 0 (Virulence Factors, Bordetella)
RN  - DH2M523P0H (Genistein)
RN  - EC 2.4.2.31 (Pertussis Toxin)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Cattle
MH  - Endothelium, Vascular/*enzymology
MH  - Enzyme Inhibitors/pharmacology
MH  - GTP-Binding Proteins/*metabolism
MH  - Genistein
MH  - Isoflavones/pharmacology
MH  - JNK Mitogen-Activated Protein Kinases
MH  - *Mitogen-Activated Protein Kinases
MH  - Pertussis Toxin
MH  - Protein-Tyrosine Kinases/metabolism
MH  - *Signal Transduction
MH  - Virulence Factors, Bordetella/pharmacology
MH  - ras Proteins/pharmacology
EDAT- 1997/01/10 00:00
MHDA- 1997/01/10 00:01
CRDT- 1997/01/10 00:00
PHST- 1997/01/10 00:00 [pubmed]
PHST- 1997/01/10 00:01 [medline]
PHST- 1997/01/10 00:00 [entrez]
AID - S0021-9258(19)77621-2 [pii]
AID - 10.1074/jbc.272.2.1395 [doi]
PST - ppublish
SO  - J Biol Chem. 1997 Jan 10;272(2):1395-401. doi: 10.1074/jbc.272.2.1395.