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...

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Autores principales:	Nada Bulus, Chloe Feral, Ambra Pozzi, Roy Zent
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7915085690a541fbbe128814a8f198e9
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spelling	oai:doaj.org-article:7915085690a541fbbe128814a8f198e92021-11-18T07:13:44ZCD98 increases renal epithelial cell proliferation by activating MAPKs.1932-620310.1371/journal.pone.0040026https://doaj.org/article/7915085690a541fbbe128814a8f198e92012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22768207/?tool=EBIhttps://doaj.org/toc/1932-6203CD98 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.Nada BulusChloe FeralAmbra PozziRoy ZentPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 6, p e40026 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nada Bulus Chloe Feral Ambra Pozzi Roy Zent CD98 increases renal epithelial cell proliferation by activating MAPKs.
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.
format	article
author	Nada Bulus Chloe Feral Ambra Pozzi Roy Zent
author_facet	Nada Bulus Chloe Feral Ambra Pozzi Roy Zent
author_sort	Nada Bulus
title	CD98 increases renal epithelial cell proliferation by activating MAPKs.
title_short	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_sort	cd98 increases renal epithelial cell proliferation by activating mapks.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/7915085690a541fbbe128814a8f198e9
work_keys_str_mv	AT nadabulus cd98increasesrenalepithelialcellproliferationbyactivatingmapks AT chloeferal cd98increasesrenalepithelialcellproliferationbyactivatingmapks AT ambrapozzi cd98increasesrenalepithelialcellproliferationbyactivatingmapks AT royzent cd98increasesrenalepithelialcellproliferationbyactivatingmapks
_version_	1718423734476341248

CD98 increases renal epithelial cell proliferation by activating MAPKs.

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