PMID- 10775131
OWN - NLM
STAT- MEDLINE
DCOM- 20000628
LR  - 20220318
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 278
IP  - 5
DP  - 2000 May
TI  - Fluid flow activates a regulator of translation, p70/p85 S6 kinase, in human 
      endothelial cells.
PG  - H1537-44
AB  - Cellular phenotype is determined not only by genetic transcription but also by 
      subsequent translation of mRNA into protein. Extracellular signals trigger 
      intracellular pathways that distinctly activate translation. The 70/85-kDa S6 
      kinase (pp70(S6k)) is a central enzyme in the signal-dependent control of 
      translation, but its regulation in endothelial cells is largely unknown. Here we 
      show that fluid flow (in the absence of an exogenous mitogen) as well as humoral 
      agonists activate endothelial pp70(S6k). Rapamycin, an inhibitor of the mammalian 
      target of rapamycin (mTOR), and wortmannin, a phosphatidylinositol 3-kinase 
      inhibitor, blocked flow-induced pp70(S6k) activation; FK-506, a rapamycin analog 
      with minimal mTOR inhibitory activity, and PD-98059, an inhibitor of the 
      flow-sensitive mitogen-activated protein kinase pathway, had no effect. Synthesis 
      of Bcl-3, a protein whose translation is controlled by an mTOR-dependent pathway, 
      was induced by flow and inhibited by rapamycin and wortmannin. Transcriptional 
      blockade did not abolish the flow-induced upregulation of Bcl-3. Fluid forces may 
      therefore modify endothelial phenotype by specifically regulating translation of 
      certain mRNA transcripts into protein.
FAU - Kraiss, L W
AU  - Kraiss LW
AD  - Division of Vascular Surgery, Department of Surgery, Eccles Institute of Human 
      Genetics, University of Utah, Salt Lake City, Utah 84112, USA. 
      larry.kraiss@hmbg.utah.edu
FAU - Weyrich, A S
AU  - Weyrich AS
FAU - Alto, N M
AU  - Alto NM
FAU - Dixon, D A
AU  - Dixon DA
FAU - Ennis, T M
AU  - Ennis TM
FAU - Modur, V
AU  - Modur V
FAU - McIntyre, T M
AU  - McIntyre TM
FAU - Prescott, S M
AU  - Prescott SM
FAU - Zimmerman, G A
AU  - Zimmerman GA
LA  - eng
GR  - HL-44525/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  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Androstadienes)
RN  - 0 (B-Cell Lymphoma 3 Protein)
RN  - 0 (BCL3 protein, human)
RN  - 0 (Bcl3 protein, mouse)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Protein Isoforms)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
RN  - WM0HAQ4WNM (Tacrolimus)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - 3T3 Cells
MH  - Androstadienes/pharmacology
MH  - Animals
MH  - B-Cell Lymphoma 3 Protein
MH  - Blood Flow Velocity/*physiology
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Endothelium, Vascular/cytology/drug effects/*enzymology
MH  - Enzyme Activation/drug effects/genetics
MH  - Humans
MH  - Immunosuppressive Agents/pharmacology
MH  - Mice
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Phosphorylation
MH  - Phosphotransferases (Alcohol Group Acceptor)/antagonists & inhibitors
MH  - Protein Isoforms/metabolism
MH  - *Protein Kinases
MH  - Proto-Oncogene Proteins/antagonists & inhibitors/biosynthesis
MH  - RNA, Messenger/biosynthesis
MH  - Ribosomal Protein S6 Kinases/genetics/*metabolism
MH  - Sirolimus/pharmacology
MH  - Stress, Mechanical
MH  - TOR Serine-Threonine Kinases
MH  - Tacrolimus/pharmacology
MH  - Transcription Factors/*metabolism
MH  - Transcription, Genetic/physiology
MH  - Viscosity
MH  - Wortmannin
EDAT- 2000/04/25 09:00
MHDA- 2000/07/06 11:00
CRDT- 2000/04/25 09:00
PHST- 2000/04/25 09:00 [pubmed]
PHST- 2000/07/06 11:00 [medline]
PHST- 2000/04/25 09:00 [entrez]
AID - 10.1152/ajpheart.2000.278.5.H1537 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2000 May;278(5):H1537-44. doi: 
      10.1152/ajpheart.2000.278.5.H1537.