Recombinant Human Leukemia inhibitory factor (LIF) (Active)

Function

Functions as a cytokine that binds to the LIF receptor complex (PubMed:11294841, PubMed:14527405, PubMed:36930708). The LIF receptor complex indeed consists of two signaling receptor subunits IL6ST/gp130 and LIFR that transduce the signal into the cell (PubMed:14527405, PubMed:36930708). Functionally, regulates cell self-renewal, differentiation and survival of embryonic stem cells (ESCs) and is crucial for embryonic implantation (By similarity). Mechanistically, ligand binding to LIFR, induces heterodimerization with IL6ST/gp130 activating JAK tyrosine kinases (JAK1 or JAK2 and to a lesser extent TYK2) bound to their intracellular domains (PubMed:11294841). These kinases subsequently phosphorylate IL6ST/gp130 and LIFR (PubMed:11294841). 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:11294841). 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:11294841). 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:11294841). 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 (By similarity). 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 GRB2-RAS-MAPK signaling (PubMed:11294841)

Subcellular Location

Secreted

• Moreau J.-F. et al. Leukaemia inhibitory factor is identical to the myeloid growth factor human interleukin for DA cells. — Nature (1988)
• Lowe D.G. et al. Genomic cloning and heterologous expression of human differentiation-stimulating factor. — DNA (1989)
• Stahl J. et al. Structural organization of the genes for murine and human leukemia inhibitory factor. Evolutionary conservation of coding and non-coding regions. — J. Biol. Chem. (1990)
• Brandenberger R. et al. Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation. — Nat. Biotechnol. (2004)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Dunham I. et al. The DNA sequence of human chromosome 22. — Nature (1999)
• Mural R.J. et al. PubMed: CI-5GBDQ6B103N1E (JUL-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)