Ganglioside GM3 activates ERKs in human lymphocytic cells
In this study we analyzed the signaling pathway triggered by GM3 in lymphoblastoid T-cells. In these cells, GM3 induced cPLA2 activation, arachidonic acid release, and PKC-δ translocation. In order to clarify the upstream molecular signals triggered by GM3, we analyzed the activation of extracellula...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2002-06-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520304727 |
| _version_ | 1818606049829060608 |
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| author | Tina Garofalo Maurizio Sorice Roberta Misasi Benedetta Cinque Vincenzo Mattei Giuseppe M. Pontieri Maria Grazia Cifone Antonio Pavan |
| author_facet | Tina Garofalo Maurizio Sorice Roberta Misasi Benedetta Cinque Vincenzo Mattei Giuseppe M. Pontieri Maria Grazia Cifone Antonio Pavan |
| author_sort | Tina Garofalo |
| collection | DOAJ |
| description | In this study we analyzed the signaling pathway triggered by GM3 in lymphoblastoid T-cells. In these cells, GM3 induced cPLA2 activation, arachidonic acid release, and PKC-δ translocation. In order to clarify the upstream molecular signals triggered by GM3, we analyzed the activation of extracellular signal-regulated kinase (ERK)s, a downstream effector of Ras-regulated cytoplasmic kinase cascade. Our results showed that GM3 treatment led to rapid ERK phosphorylation in lymphoblastoid T-cells, as detected by anti-phospho-p44/42 MAP kinase. Similar findings were found in human peripheral blood lymphocytes. Moreover, we showed that GM3 specifically phosphorylated ERK-2, as revealed by anti-phosphotyrosine reactivity on both cell free lysates and ERKs immunoprecipitates. The role of the CD4 cytoplasmic domain in GM3-triggered signaling pathway was investigated using A2.01/CD4-cyt399 cells, which had been transfected with a mutant form of CD4 lacking the bulk of the cytoplasmic domain. In these cells GM3 induced cPLA2 activation, arachidonic acid release, and PKC-δ translocation, but not CD4 endocytosis, indicating that the CD4 cytoplasmic domain plays a key role in GM3-triggered CD4 endocytosis and the GM3-triggered biochemical pathway is upstream of CD4 phosphorylation.These findings strongly suggest that GM3 triggers a novel signaling pathway involved in the regulation of cellular functions. |
| first_indexed | 2024-12-16T14:04:41Z |
| format | Article |
| id | doaj.art-68f2aae6c60146e5be07331bd10addd4 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-16T14:04:41Z |
| publishDate | 2002-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-68f2aae6c60146e5be07331bd10addd42022-12-21T22:28:57ZengElsevierJournal of Lipid Research0022-22752002-06-01436971978Ganglioside GM3 activates ERKs in human lymphocytic cellsTina Garofalo0Maurizio Sorice1Roberta Misasi2Benedetta Cinque3Vincenzo Mattei4Giuseppe M. Pontieri5Maria Grazia Cifone6Antonio Pavan7Dipartimento di Medicina Sperimentale e Patologia, Università di Roma “La Sapienza,” Viale Regina Elena 324, Roma 00161, ItalyDipartimento di Medicina Sperimentale e Patologia, Università di Roma “La Sapienza,” Viale Regina Elena 324, Roma 00161, ItalyDipartimento di Medicina Sperimentale e Patologia, Università di Roma “La Sapienza,” Viale Regina Elena 324, Roma 00161, ItalyDipartimento di Medicina Sperimentale, Università di L'Aquila, Via Vetoio Coppito 2, L'Aquila 67100, ItalyDipartimento di Medicina Sperimentale e Patologia, Università di Roma “La Sapienza,” Viale Regina Elena 324, Roma 00161, ItalyDipartimento di Medicina Sperimentale e Patologia, Università di Roma “La Sapienza,” Viale Regina Elena 324, Roma 00161, ItalyDipartimento di Medicina Sperimentale, Università di L'Aquila, Via Vetoio Coppito 2, L'Aquila 67100, ItalyDipartimento di Medicina Sperimentale, Università di L'Aquila, Via Vetoio Coppito 2, L'Aquila 67100, ItalyIn this study we analyzed the signaling pathway triggered by GM3 in lymphoblastoid T-cells. In these cells, GM3 induced cPLA2 activation, arachidonic acid release, and PKC-δ translocation. In order to clarify the upstream molecular signals triggered by GM3, we analyzed the activation of extracellular signal-regulated kinase (ERK)s, a downstream effector of Ras-regulated cytoplasmic kinase cascade. Our results showed that GM3 treatment led to rapid ERK phosphorylation in lymphoblastoid T-cells, as detected by anti-phospho-p44/42 MAP kinase. Similar findings were found in human peripheral blood lymphocytes. Moreover, we showed that GM3 specifically phosphorylated ERK-2, as revealed by anti-phosphotyrosine reactivity on both cell free lysates and ERKs immunoprecipitates. The role of the CD4 cytoplasmic domain in GM3-triggered signaling pathway was investigated using A2.01/CD4-cyt399 cells, which had been transfected with a mutant form of CD4 lacking the bulk of the cytoplasmic domain. In these cells GM3 induced cPLA2 activation, arachidonic acid release, and PKC-δ translocation, but not CD4 endocytosis, indicating that the CD4 cytoplasmic domain plays a key role in GM3-triggered CD4 endocytosis and the GM3-triggered biochemical pathway is upstream of CD4 phosphorylation.These findings strongly suggest that GM3 triggers a novel signaling pathway involved in the regulation of cellular functions.http://www.sciencedirect.com/science/article/pii/S0022227520304727extracellular signal-regulated kinaseCD4lipid domainsglycosphingolipids |
| spellingShingle | Tina Garofalo Maurizio Sorice Roberta Misasi Benedetta Cinque Vincenzo Mattei Giuseppe M. Pontieri Maria Grazia Cifone Antonio Pavan Ganglioside GM3 activates ERKs in human lymphocytic cells Journal of Lipid Research extracellular signal-regulated kinase CD4 lipid domains glycosphingolipids |
| title | Ganglioside GM3 activates ERKs in human lymphocytic cells |
| title_full | Ganglioside GM3 activates ERKs in human lymphocytic cells |
| title_fullStr | Ganglioside GM3 activates ERKs in human lymphocytic cells |
| title_full_unstemmed | Ganglioside GM3 activates ERKs in human lymphocytic cells |
| title_short | Ganglioside GM3 activates ERKs in human lymphocytic cells |
| title_sort | ganglioside gm3 activates erks in human lymphocytic cells |
| topic | extracellular signal-regulated kinase CD4 lipid domains glycosphingolipids |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520304727 |
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