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INTEGRATION OF SIGNAL PATHWAYS FOR STRETCH-DEPENDENT GROWTH AND DIFFERENTIATION IN VASCULAR SMOOTH MUSCLE.

Albinsson, Sebastian LU and Hellstrand, Per LU (2007) In American Journal of Physiology: Cell Physiology 293(May 16). p.772-782
Abstract
Vascular smooth muscle phenotype is regulated by environmental factors, such as mechanical forces, which exert effects on signaling to differentiation and growth. We used the mouse portal vein in organ culture to investigate stretch-dependent activation of Akt, extracellular regulated protein kinase (ERK) and focal adhesion kinase (FAK), which have been suggested to be involved in the regulation of stretch-dependent protein synthesis. The role of actin polymerization in these signaling events was examined using the actin stabilizing agent jasplakinolide. Stretch caused a biphasic activation of FAK at 5-15 minutes and 24-72 hours, which may reflect first a direct phosphorylation of preexisting focal adhesions followed by a rearrangement of... (More)
Vascular smooth muscle phenotype is regulated by environmental factors, such as mechanical forces, which exert effects on signaling to differentiation and growth. We used the mouse portal vein in organ culture to investigate stretch-dependent activation of Akt, extracellular regulated protein kinase (ERK) and focal adhesion kinase (FAK), which have been suggested to be involved in the regulation of stretch-dependent protein synthesis. The role of actin polymerization in these signaling events was examined using the actin stabilizing agent jasplakinolide. Stretch caused a biphasic activation of FAK at 5-15 minutes and 24-72 hours, which may reflect first a direct phosphorylation of preexisting focal adhesions followed by a rearrangement of focal adhesions to accommodate for the increased mechanical load. Phosphorylation of ERK was increased by acute stretch but then decreased, and Akt did not have a distinct peak in stretch-induced phosphorylation. Inhibition of ERK, phosphatidylinositol 3-kinase (PI3K) or mammalian target of rapamycin (mTOR) reduced global but not contractile protein synthesis with maintained stretch sensitivity. Stabilization of actin filaments with jasplakinolide, in unstretched portal veins, resulted in increased ERK phosphorylation and global protein synthesis as well as synthesis of contractile proteins. In contrast, stretch during culture with jasplakinolide did not affect FAK phosphorylation or contractility. Therefore, remodeling of smooth muscle cells to adapt to stretch requires a dynamic cytoskeleton. Key words: actin polymerization, MAP kinase, PI3 kinase, focal adhesion kinase, protein synthesis. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
phosphatidylinositol 3-kinase, protein synthesis, actin polymerization, mitogen-activated protein kinase, focal adhesion kinase
in
American Journal of Physiology: Cell Physiology
volume
293
issue
May 16
pages
772 - 782
publisher
American Physiological Society
external identifiers
  • wos:000248581000027
  • scopus:34547822405
ISSN
1522-1563
DOI
10.1152/ajpcell.00622.2006
language
English
LU publication?
yes
id
d22c802f-c072-41f1-a772-2a1ab5227f73 (old id 168253)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17507430&dopt=Abstract
date added to LUP
2007-07-09 16:07:06
date last changed
2017-08-27 05:30:25
@article{d22c802f-c072-41f1-a772-2a1ab5227f73,
  abstract     = {Vascular smooth muscle phenotype is regulated by environmental factors, such as mechanical forces, which exert effects on signaling to differentiation and growth. We used the mouse portal vein in organ culture to investigate stretch-dependent activation of Akt, extracellular regulated protein kinase (ERK) and focal adhesion kinase (FAK), which have been suggested to be involved in the regulation of stretch-dependent protein synthesis. The role of actin polymerization in these signaling events was examined using the actin stabilizing agent jasplakinolide. Stretch caused a biphasic activation of FAK at 5-15 minutes and 24-72 hours, which may reflect first a direct phosphorylation of preexisting focal adhesions followed by a rearrangement of focal adhesions to accommodate for the increased mechanical load. Phosphorylation of ERK was increased by acute stretch but then decreased, and Akt did not have a distinct peak in stretch-induced phosphorylation. Inhibition of ERK, phosphatidylinositol 3-kinase (PI3K) or mammalian target of rapamycin (mTOR) reduced global but not contractile protein synthesis with maintained stretch sensitivity. Stabilization of actin filaments with jasplakinolide, in unstretched portal veins, resulted in increased ERK phosphorylation and global protein synthesis as well as synthesis of contractile proteins. In contrast, stretch during culture with jasplakinolide did not affect FAK phosphorylation or contractility. Therefore, remodeling of smooth muscle cells to adapt to stretch requires a dynamic cytoskeleton. Key words: actin polymerization, MAP kinase, PI3 kinase, focal adhesion kinase, protein synthesis.},
  author       = {Albinsson, Sebastian and Hellstrand, Per},
  issn         = {1522-1563},
  keyword      = {phosphatidylinositol 3-kinase,protein synthesis,actin polymerization,mitogen-activated protein kinase,focal adhesion kinase},
  language     = {eng},
  number       = {May 16},
  pages        = {772--782},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology: Cell Physiology},
  title        = {INTEGRATION OF SIGNAL PATHWAYS FOR STRETCH-DEPENDENT GROWTH AND DIFFERENTIATION IN VASCULAR SMOOTH MUSCLE.},
  url          = {http://dx.doi.org/10.1152/ajpcell.00622.2006},
  volume       = {293},
  year         = {2007},
}