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Fibroblast growth factor–specific modulation of cellular response by syndecan-4

Proteoglycans participate in growth factor interaction with the cell surface through their heparan sulfate chains (HS), but it is not known if they are otherwise involved in growth factor signaling. It appears now that the syndecan-4 core protein, a transmembrane proteoglycan shown previously to bin...

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Detalles Bibliográficos
Autores principales: Horowitz, Arie, Tkachenko, Eugene, Simons, Michael
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2002
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173870/
https://www.ncbi.nlm.nih.gov/pubmed/12011116
http://dx.doi.org/10.1083/jcb.200112145
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author Horowitz, Arie
Tkachenko, Eugene
Simons, Michael
author_facet Horowitz, Arie
Tkachenko, Eugene
Simons, Michael
author_sort Horowitz, Arie
collection PubMed
description Proteoglycans participate in growth factor interaction with the cell surface through their heparan sulfate chains (HS), but it is not known if they are otherwise involved in growth factor signaling. It appears now that the syndecan-4 core protein, a transmembrane proteoglycan shown previously to bind phosphatidylinositol 4,5-bisphosphate (PIP(2)) and activate PKCα, participates in mediating the effects of fibroblast growth factor (FGF)2 on cell function. Mutations in the cytoplasmic tail of syndecan-4 that either reduced its affinity to PIP(2) (PIP(2) (−)) or disrupted its postsynaptic density 95, disk large, zona occludens-1 (PDZ)-dependent binding (PDZ(−)) produced a FGF2-specific dominant negative phenotype in endothelial cells as evidenced by the marked decline of their migration and proliferation rates and the impairment of their capacity to form tubes. In both cases, the molecular mechanism was determined to consist of a decrease in the syndecan-4–dependent activation of PKCα. This decrease was caused either by inhibition of FGF2-induced syndecan-4 dephosphorylation in the case of the PDZ(−) mutation or by disruption of basolateral targeting of syndecan-4 and its associated PDZ-dependent complex in the case of the PIP(2) (−) mutation. These results suggest that PKCα activation and PDZ-mediated formation of a serine/threonine phosphatase-containing complex by syndecan-4 are downstream events of FGF2 signaling.
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spelling pubmed-21738702008-05-01 Fibroblast growth factor–specific modulation of cellular response by syndecan-4 Horowitz, Arie Tkachenko, Eugene Simons, Michael J Cell Biol Article Proteoglycans participate in growth factor interaction with the cell surface through their heparan sulfate chains (HS), but it is not known if they are otherwise involved in growth factor signaling. It appears now that the syndecan-4 core protein, a transmembrane proteoglycan shown previously to bind phosphatidylinositol 4,5-bisphosphate (PIP(2)) and activate PKCα, participates in mediating the effects of fibroblast growth factor (FGF)2 on cell function. Mutations in the cytoplasmic tail of syndecan-4 that either reduced its affinity to PIP(2) (PIP(2) (−)) or disrupted its postsynaptic density 95, disk large, zona occludens-1 (PDZ)-dependent binding (PDZ(−)) produced a FGF2-specific dominant negative phenotype in endothelial cells as evidenced by the marked decline of their migration and proliferation rates and the impairment of their capacity to form tubes. In both cases, the molecular mechanism was determined to consist of a decrease in the syndecan-4–dependent activation of PKCα. This decrease was caused either by inhibition of FGF2-induced syndecan-4 dephosphorylation in the case of the PDZ(−) mutation or by disruption of basolateral targeting of syndecan-4 and its associated PDZ-dependent complex in the case of the PIP(2) (−) mutation. These results suggest that PKCα activation and PDZ-mediated formation of a serine/threonine phosphatase-containing complex by syndecan-4 are downstream events of FGF2 signaling. The Rockefeller University Press 2002-05-13 /pmc/articles/PMC2173870/ /pubmed/12011116 http://dx.doi.org/10.1083/jcb.200112145 Text en Copyright © 2002, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Horowitz, Arie
Tkachenko, Eugene
Simons, Michael
Fibroblast growth factor–specific modulation of cellular response by syndecan-4
title Fibroblast growth factor–specific modulation of cellular response by syndecan-4
title_full Fibroblast growth factor–specific modulation of cellular response by syndecan-4
title_fullStr Fibroblast growth factor–specific modulation of cellular response by syndecan-4
title_full_unstemmed Fibroblast growth factor–specific modulation of cellular response by syndecan-4
title_short Fibroblast growth factor–specific modulation of cellular response by syndecan-4
title_sort fibroblast growth factor–specific modulation of cellular response by syndecan-4
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173870/
https://www.ncbi.nlm.nih.gov/pubmed/12011116
http://dx.doi.org/10.1083/jcb.200112145
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