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The Csk-binding protein PAG regulates PDGF-induced Src mitogenic signaling via GM1
Spatial regulation is an important feature of signal specificity elicited by cytoplasmic tyrosine kinases of the Src family (SRC family protein tyrosine kinases [SFK]). Cholesterol-enriched membrane domains, such as caveolae, regulate association of SFK with the platelet-derived growth factor recept...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2500143/ https://www.ncbi.nlm.nih.gov/pubmed/18695048 http://dx.doi.org/10.1083/jcb.200705102 |
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author | Veracini, Laurence Simon, Valérie Richard, Véronique Schraven, Burkhart Horejsi, Vaclav Roche, Serge Benistant, Christine |
author_facet | Veracini, Laurence Simon, Valérie Richard, Véronique Schraven, Burkhart Horejsi, Vaclav Roche, Serge Benistant, Christine |
author_sort | Veracini, Laurence |
collection | PubMed |
description | Spatial regulation is an important feature of signal specificity elicited by cytoplasmic tyrosine kinases of the Src family (SRC family protein tyrosine kinases [SFK]). Cholesterol-enriched membrane domains, such as caveolae, regulate association of SFK with the platelet-derived growth factor receptor (PDGFR), which is needed for kinase activation and mitogenic signaling. PAG, a ubiquitously expressed member of the transmembrane adaptor protein family, is known to negatively regulate SFK signaling though binding to Csk. We report that PAG modulates PDGFR levels in caveolae and SFK mitogenic signaling through a Csk-independent mechanism. Regulation of SFK mitogenic activity by PAG requires the first N-terminal 97 aa (PAG-N), which include the extracellular and transmembrane domains, palmitoylation sites, and a short cytoplasmic sequence. We also show that PAG-N increases ganglioside GM1 levels at the cell surface and, thus, displaces PDGFR from caveolae, a process that requires the ganglioside-specific sialidase Neu-3. In conclusion, PAG regulates PDGFR membrane partitioning and SFK mitogenic signaling by modulating GM1 levels within caveolae independently from Csk. |
format | Text |
id | pubmed-2500143 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-25001432009-02-11 The Csk-binding protein PAG regulates PDGF-induced Src mitogenic signaling via GM1 Veracini, Laurence Simon, Valérie Richard, Véronique Schraven, Burkhart Horejsi, Vaclav Roche, Serge Benistant, Christine J Cell Biol Research Articles Spatial regulation is an important feature of signal specificity elicited by cytoplasmic tyrosine kinases of the Src family (SRC family protein tyrosine kinases [SFK]). Cholesterol-enriched membrane domains, such as caveolae, regulate association of SFK with the platelet-derived growth factor receptor (PDGFR), which is needed for kinase activation and mitogenic signaling. PAG, a ubiquitously expressed member of the transmembrane adaptor protein family, is known to negatively regulate SFK signaling though binding to Csk. We report that PAG modulates PDGFR levels in caveolae and SFK mitogenic signaling through a Csk-independent mechanism. Regulation of SFK mitogenic activity by PAG requires the first N-terminal 97 aa (PAG-N), which include the extracellular and transmembrane domains, palmitoylation sites, and a short cytoplasmic sequence. We also show that PAG-N increases ganglioside GM1 levels at the cell surface and, thus, displaces PDGFR from caveolae, a process that requires the ganglioside-specific sialidase Neu-3. In conclusion, PAG regulates PDGFR membrane partitioning and SFK mitogenic signaling by modulating GM1 levels within caveolae independently from Csk. The Rockefeller University Press 2008-08-11 /pmc/articles/PMC2500143/ /pubmed/18695048 http://dx.doi.org/10.1083/jcb.200705102 Text en © 2008 Veracini et al. 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.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Veracini, Laurence Simon, Valérie Richard, Véronique Schraven, Burkhart Horejsi, Vaclav Roche, Serge Benistant, Christine The Csk-binding protein PAG regulates PDGF-induced Src mitogenic signaling via GM1 |
title | The Csk-binding protein PAG regulates PDGF-induced Src mitogenic signaling via GM1 |
title_full | The Csk-binding protein PAG regulates PDGF-induced Src mitogenic signaling via GM1 |
title_fullStr | The Csk-binding protein PAG regulates PDGF-induced Src mitogenic signaling via GM1 |
title_full_unstemmed | The Csk-binding protein PAG regulates PDGF-induced Src mitogenic signaling via GM1 |
title_short | The Csk-binding protein PAG regulates PDGF-induced Src mitogenic signaling via GM1 |
title_sort | csk-binding protein pag regulates pdgf-induced src mitogenic signaling via gm1 |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2500143/ https://www.ncbi.nlm.nih.gov/pubmed/18695048 http://dx.doi.org/10.1083/jcb.200705102 |
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