The Csk-binding protein PAG regulates PDGF-induced Src mitogenic signaling via GM1
| العنوان: | The Csk-binding protein PAG regulates PDGF-induced Src mitogenic signaling via GM1 |
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| المؤلفون: | Burkhart Schraven, Véronique Richard, Christine Benistant, Valérie Simon, Laurence Veracini, Vaclav Horejsi, Serge Roche |
| المساهمون: | Centre de recherche en Biologie Cellulaire (CRBM), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Otto-von-Guericke University [Magdeburg] (OVGU), Institute of Molecular Genetics of the Czech Academy of Sciences (IMG / CAS), Czech Academy of Sciences [Prague] (CAS) |
| المصدر: | Journal of Cell Biology Journal of Cell Biology, Rockefeller University Press, 2008, 182 (3), pp.603-14. ⟨10.1083/jcb.200705102⟩ The Journal of Cell Biology |
| بيانات النشر: | HAL CCSD, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | MESH: Signal Transduction, CSK Tyrosine-Protein Kinase, Mice, 0302 clinical medicine, Caveolae, Receptors, Platelet-Derived Growth Factor, MESH: Animals, MESH: Receptors, Platelet-Derived Growth Factor, Research Articles, Platelet-Derived Growth Factor, 0303 health sciences, biology, MESH: G(M1) Ganglioside, MESH: Platelet-Derived Growth Factor, MESH: DNA, Signal transducing adaptor protein, MESH: Neuraminidase, MESH: Mitogens, Protein-Tyrosine Kinases, Cell biology, src-Family Kinases, 030220 oncology & carcinogenesis, MESH: Caveolae, Intercellular Signaling Peptides and Proteins, MESH: Membrane Proteins, Signal transduction, Tyrosine kinase, Platelet-derived growth factor receptor, Protein Binding, Signal Transduction, Proto-oncogene tyrosine-protein kinase Src, Proto-Oncogene Proteins pp60(c-src), Neuraminidase, G(M1) Ganglioside, Models, Biological, MESH: Phosphoproteins, MESH: Protein-Tyrosine Kinases, Article, 03 medical and health sciences, Palmitoylation, Animals, Humans, MESH: Protein Binding, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, 030304 developmental biology, MESH: Humans, MESH: Models, Biological, Membrane Proteins, Adaptor Signaling Protein, DNA, Cell Biology, MESH: Proto-Oncogene Proteins pp60(c-src), Phosphoproteins, nervous system, NIH 3T3 Cells, biology.protein, Mitogens, MESH: NIH 3T3 Cells |
| الوصف: | International audience; 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. |
| اللغة: | English |
| تدمد: | 0021-9525 1540-8140 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0272656859180280eda9fd272d239a8c https://hal.archives-ouvertes.fr/hal-00348407 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....0272656859180280eda9fd272d239a8c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00219525 15408140 |
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