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LIF-dependent survival of embryonic stem cells is regulated by a novel palmitoylated Gab1 signalling protein.

Published version
Peer-reviewed

Type

Article

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Authors

Sutherland, Linda 
Ruhe, Madeleine 
Gattegno-Ho, Daniela  ORCID logo  https://orcid.org/0000-0002-0980-0165
Greaves, Jennifer 

Abstract

The cytokine leukaemia inhibitory factor (LIF) promotes self-renewal of mouse embryonic stem cells (ESCs) through activation of the transcription factor Stat3. However, the contribution of other ancillary pathways stimulated by LIF in ESCs, such as the MAPK and PI3K pathways, is less well understood. We show here that naive-type mouse ESCs express high levels of a novel effector of the MAPK and PI3K pathways. This effector is an isoform of the Gab1 (Grb2-associated binder protein 1) adaptor protein that lacks the N-terminal pleckstrin homology (PH) membrane-binding domain. Although not essential for rapid unrestricted growth of ESCs under optimal conditions, the novel Gab1 variant (Gab1β) is required for LIF-mediated cell survival under conditions of limited nutrient availability. This enhanced survival is absolutely dependent upon a latent palmitoylation site that targets Gab1β directly to ESC membranes. These results show that constitutive association of Gab1 with membranes through a novel mechanism promotes LIF-dependent survival of murine ESCs in nutrient-poor conditions.

Description

Keywords

Embryonic stem cells, Gab1, Leukaemia inhibitory factor, Palmitoylation, Stem cell survival, Adaptor Proteins, Signal Transducing, Animals, Cells, Cultured, Embryonic Stem Cells, Leukemia Inhibitory Factor, Signal Transduction

Journal Title

J Cell Sci

Conference Name

Journal ISSN

0021-9533
1477-9137

Volume Title

131

Publisher

The Company of Biologists
Sponsorship
MRC (G1100526)