Requirement of Caveolae Microdomains in Extracellular Signal‐Regulated Kinase and Focal Adhesion Kinase Activation Induced by Endothelin‐1 in Primary Astrocytes

Requirement of Caveolae Microdomains in Extracellular Signal‐Regulated Kinase and Focal... Abstract : Endothelin‐1 (ET‐1) mitogenic activity in astrocytes is mediated by the activation of the extracellular signal‐regulated kinase (ERK) pathway together with the Rho‐dependent activation of the focal adhesion kinase (FAK) pathway. To clarify the mechanisms responsible for the coordinate activation of both pathways in the ET‐1 signal propagation, the involvement of caveolae microdomains, suggested to play a role in signal transduction, was evaluated. In this study, it is reported that caveolae of primary astrocytes are enriched in endothelin receptor (ETB‐R). Furthermore, signaling molecules such as the adaptor proteins Shc and Grb2, and the small G protein Rho, also reside within these microdomains. Selective disassembly of caveolae by filipin III impairs the ET‐1‐induced tyrosine phosphorylation of proteins including ERK and FAK. In agreement with these observations, astrocytes pretreated with filipin III also failed to form stress fibers and focal adhesions and did not undergo the associated morphological changes in response to ET‐1. This study reveals that structural integrity of caveolae is necessary for the adhesion‐dependent mitogenic signals induced by ET‐1 in astrocytes, through compartmentation of ETB‐R with the upstream signaling molecules of the ERK and FAK pathways. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neurochemistry Wiley

Requirement of Caveolae Microdomains in Extracellular Signal‐Regulated Kinase and Focal Adhesion Kinase Activation Induced by Endothelin‐1 in Primary Astrocytes

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Publisher
Wiley Subscription Services, Inc., A Wiley Company
Copyright
© International Society for Neurochemistry
ISSN
0022-3042
eISSN
1471-4159
D.O.I.
10.1046/j.1471-4159.1999.0720120.x
Publisher site
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Abstract

Abstract : Endothelin‐1 (ET‐1) mitogenic activity in astrocytes is mediated by the activation of the extracellular signal‐regulated kinase (ERK) pathway together with the Rho‐dependent activation of the focal adhesion kinase (FAK) pathway. To clarify the mechanisms responsible for the coordinate activation of both pathways in the ET‐1 signal propagation, the involvement of caveolae microdomains, suggested to play a role in signal transduction, was evaluated. In this study, it is reported that caveolae of primary astrocytes are enriched in endothelin receptor (ETB‐R). Furthermore, signaling molecules such as the adaptor proteins Shc and Grb2, and the small G protein Rho, also reside within these microdomains. Selective disassembly of caveolae by filipin III impairs the ET‐1‐induced tyrosine phosphorylation of proteins including ERK and FAK. In agreement with these observations, astrocytes pretreated with filipin III also failed to form stress fibers and focal adhesions and did not undergo the associated morphological changes in response to ET‐1. This study reveals that structural integrity of caveolae is necessary for the adhesion‐dependent mitogenic signals induced by ET‐1 in astrocytes, through compartmentation of ETB‐R with the upstream signaling molecules of the ERK and FAK pathways.

Journal

Journal of NeurochemistryWiley

Published: Jan 1, 1999

Keywords: ; ; ; ; ;

References

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