TY - JOUR
T1 - LIF-dependent survival of embryonic stem cells is regulated by a novel palmitoylated Gab1 signalling protein
AU - Sutherland, Linda
AU - Ruhe, Madeleine
AU - Gattegno-Ho, Daniela
AU - Mann, Karanjit
AU - Greaves, Jennifer
AU - Koscielniak, Magdalena
AU - Meek, Stephen
AU - Lu, Zen
AU - Waterfall, Martin
AU - Taylor, Ryan
AU - Tsakiridis, Anestis
AU - Brown, Helen
AU - Maciver, Sutherland K.
AU - Joshi, Anagha
AU - Clinton, Michael
AU - Chamberlain, Luke H.
AU - Smith, Austin
AU - Burdon, Tom
PY - 2018/9/20
Y1 - 2018/9/20
N2 - 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.
AB - 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.
KW - leukaemia inhibitory factor
KW - Gab1
KW - embryonic stem cells
KW - palmitoylation
KW - stem cell survival
UR - http://jcs.biologists.org/
U2 - 10.1242/jcs.222257
DO - 10.1242/jcs.222257
M3 - Article
SN - 0021-9533
VL - 131
JO - Journal of Cell Science
JF - Journal of Cell Science
IS - 18
ER -
