CD98 increases renal epithelial cell proliferation by activating MAPKs.
CD98 heavy chain (CD98hc) is a multifunctional transmembrane spanning scaffolding protein whose extracellular domain binds with light chain amino acid transporters (Lats) to form the heterodimeric amino acid transporters (HATs). It also interacts with β1 and β3 integrins by its transmembrane and cyt...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22768207/?tool=EBI |
| _version_ | 1818458862025441280 |
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| author | Nada Bulus Chloe Feral Ambra Pozzi Roy Zent |
| author_facet | Nada Bulus Chloe Feral Ambra Pozzi Roy Zent |
| author_sort | Nada Bulus |
| collection | DOAJ |
| description | CD98 heavy chain (CD98hc) is a multifunctional transmembrane spanning scaffolding protein whose extracellular domain binds with light chain amino acid transporters (Lats) to form the heterodimeric amino acid transporters (HATs). It also interacts with β1 and β3 integrins by its transmembrane and cytoplasmic domains. This interaction is proposed to be the mechanism whereby CD98 mediates cell survival and growth via currently undefined signaling pathways. In this study, we determined whether the critical function of CD98-dependent amino acid transport also plays a role in cell proliferation and defined the signaling pathways that mediate CD98-dependent proliferation of murine renal inner medullary collecting duct (IMCD) cells. We demonstrate that downregulating CD98hc expression resulted in IMCD cell death. Utilizing overexpression studies of CD98hc mutants that either lacked a cytoplasmic tail or were unable to bind to Lats we showed that CD98 increases serum-dependent cell proliferation by a mechanism that requires the CD98hc cytoplasmic tail. We further demonstrated that CD98-dependent amino acid transport increased renal tubular epithelial cell proliferation by a mechanism that does not require the CD98hc cytoplasmic tail. Both these mechanisms of increased renal tubular epithelial cell proliferation are mediated by Erk and p38 MAPK signaling. Although increased amino transport markedly activated mTor signaling, this pathway did not alter cell proliferation. Thus, these studies demonstrate that in IMCD cells, the cytoplasmic and extracellular domains of CD98hc regulate cell proliferation by distinct mechanisms that are mediated by common MAPK signaling pathways. |
| first_indexed | 2024-12-14T23:05:12Z |
| format | Article |
| id | doaj.art-7915085690a541fbbe128814a8f198e9 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T23:05:12Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-7915085690a541fbbe128814a8f198e92022-12-21T22:44:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0176e4002610.1371/journal.pone.0040026CD98 increases renal epithelial cell proliferation by activating MAPKs.Nada BulusChloe FeralAmbra PozziRoy ZentCD98 heavy chain (CD98hc) is a multifunctional transmembrane spanning scaffolding protein whose extracellular domain binds with light chain amino acid transporters (Lats) to form the heterodimeric amino acid transporters (HATs). It also interacts with β1 and β3 integrins by its transmembrane and cytoplasmic domains. This interaction is proposed to be the mechanism whereby CD98 mediates cell survival and growth via currently undefined signaling pathways. In this study, we determined whether the critical function of CD98-dependent amino acid transport also plays a role in cell proliferation and defined the signaling pathways that mediate CD98-dependent proliferation of murine renal inner medullary collecting duct (IMCD) cells. We demonstrate that downregulating CD98hc expression resulted in IMCD cell death. Utilizing overexpression studies of CD98hc mutants that either lacked a cytoplasmic tail or were unable to bind to Lats we showed that CD98 increases serum-dependent cell proliferation by a mechanism that requires the CD98hc cytoplasmic tail. We further demonstrated that CD98-dependent amino acid transport increased renal tubular epithelial cell proliferation by a mechanism that does not require the CD98hc cytoplasmic tail. Both these mechanisms of increased renal tubular epithelial cell proliferation are mediated by Erk and p38 MAPK signaling. Although increased amino transport markedly activated mTor signaling, this pathway did not alter cell proliferation. Thus, these studies demonstrate that in IMCD cells, the cytoplasmic and extracellular domains of CD98hc regulate cell proliferation by distinct mechanisms that are mediated by common MAPK signaling pathways.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22768207/?tool=EBI |
| spellingShingle | Nada Bulus Chloe Feral Ambra Pozzi Roy Zent CD98 increases renal epithelial cell proliferation by activating MAPKs. PLoS ONE |
| title | CD98 increases renal epithelial cell proliferation by activating MAPKs. |
| title_full | CD98 increases renal epithelial cell proliferation by activating MAPKs. |
| title_fullStr | CD98 increases renal epithelial cell proliferation by activating MAPKs. |
| title_full_unstemmed | CD98 increases renal epithelial cell proliferation by activating MAPKs. |
| title_short | CD98 increases renal epithelial cell proliferation by activating MAPKs. |
| title_sort | cd98 increases renal epithelial cell proliferation by activating mapks |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22768207/?tool=EBI |
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