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The cleaved FAS ligand activates the Na+/H+ exchanger NHE1 through Akt/ROCK1 to stimulate cell motility

Abstract : Transmembrane CD95L (Fas ligand) can be cleaved to release a promigratory soluble ligand, cl-CD95L, which can contribute to chronic inflammation and cancer cell dissemination. The motility signaling pathway elicited by cl-CD95L remains poorly defined. Here, we show that in the presence of cl-CD95L, CD95 activates the Akt and RhoA signaling pathways, which together orchestrate an allosteric activation of the Na+/H+ exchanger NHE1. Pharmacologic inhibition of Akt or ROCK1 independently blocks the cl-CD95L-induced migration. Confirming these pharmacologic data, disruption of the Akt and ROCK1 phosphorylation sites on NHE1 decreases cell migration in cells exposed to cl-CD95L. Together, these findings demonstrate that NHE1 is a novel molecular actor in the CD95 signaling pathway that drives the cl-CD95L-induced cell migration through both the Akt and RhoA signaling pathways.
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https://hal-univ-rennes1.archives-ouvertes.fr/hal-01334067
Contributor : Laurent Jonchère <>
Submitted on : Friday, November 25, 2016 - 3:42:56 PM
Last modification on : Wednesday, October 14, 2020 - 4:22:53 AM

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Michaël Monet, Mallorie Poet, Sébastien Tauzin, Amelie Fouque, Auréa Cophignon, et al.. The cleaved FAS ligand activates the Na+/H+ exchanger NHE1 through Akt/ROCK1 to stimulate cell motility. Scientific Reports, Nature Publishing Group, 2016, 6 (1), pp.28008. ⟨10.1038/srep28008⟩. ⟨hal-01334067⟩

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