The cytokine leukaemia inhibitory factor (LIF) promotes self-renewal of murine embryonic stem cells (ESCs) mainly through activation of the transcription factor Stat3. The role of other signalling pathways activated by the LIF receptor in ESCs, however, is less well characterised. Here (Sutherland et al., 2018), Tom Burdon and colleagues identify a new variant form of the adaptor protein Gab1 that contributes to LIF-dependent survival of ESCs when nutrient availability is limited. The authors show that mouse ESCs express a short form of Gab1, termed Gab1β, that lacks the N-terminal PH membrane-binding domain, but still contributes to signalling downstream of LIFR in ESCs. The authors find that expression of Gab1β in ESCs promotes cell survival in a LIF-dependent manner in nutrient-depleted conditions, and further, that membrane localisation of Gab1β is essential for its survival function and is dependent on its palmitoylation. This paper reports the identification of a new variant form of the adaptor protein Gab1 that is constitutively associated with ESC membranes and supports LIF-dependent survival under conditions of limited nutrient availability.
