Recombinant Mouse Leukemia inhibitory factor (Lif) (Active)

Function

Functions as a cytokine that binds to the LIF receptor complex (By similarity). The LIF receptor complex indeed consists of two signaling receptor subunits IL6ST/gp130 and LIFR that transduce the signal into the cell (By similarity). Functionally, regulates cell self-renewal, differentiation and survival of embryonic stem cells (EScs) and is crucial for embryonic implantation (PubMed:1522892, PubMed:16452727, PubMed:26775702, PubMed:3127201, PubMed:3143916). Mechanistically, ligand binding to LIFR, induces heterodimerization with IL6ST/gp130 activating JAK tyrosine kinases (JAK1 or JAK2 and to lesser extent TYK2) bound to their intracellular domains (PubMed:8921810). These kinases subsequently phosphorylate IL6ST/gp130 and LIFR (PubMed:8921810). The tyrosine phosphorylated signaling receptors serve in turn as docking sites for recruitment and activation of signal transducers and activators of transcription (STAT3 and to lesser extent STAT1) (PubMed:8921810). In parallel to the activation of the STAT3-pathway, the binding of LIF to the LIF receptor complex leads to the activation of the mitogen-activated protein kinase (MAPK) and the phosphatidylinositol 3-kinase (PI(3)K) pathways (PubMed:15328362, PubMed:9545305). Tyrosine phosphorylation of the p85 subunit of PI(3)K by JAK1 leads to activation of the serine/ threonine kinase AKT (protein kinase B) (PubMed:9545305). PI(3)K-dependent signaling is required for efficient self-renewal of murine ES cells, and regulation of ERK activity is functionally important in this response (PubMed:15328362). Moreover, induces tyrosine phosphorylation of PTPN11, that associates with IL6ST/gp130-LIFR, which in turn recruits the p85 regulatory subunit of PI(3)K protein kinase, promoting PI3K-AKT activation, and (in many systems) GRB2-RAS-MAPK signaling (By similarity)