LIF
LIF (leukaemia inhibitory factor) is a secreted, pleiotropic cytokine of the interleukin 6 family that signals through the LIF receptor complex. Also known as CDF, DIA and HILDA, it regulates stem cell self-renewal, differentiation and survival. Browse Assay Genie's current range of LIF research reagents below, or read on for the biology behind the target.
LIF functions as a cytokine that binds the LIF receptor complex, which is made up of two signalling subunits, LIFR and IL6ST (gp130). Ligand binding to LIFR induces heterodimerisation with IL6ST, activating the JAK tyrosine kinases bound to their intracellular domains: JAK1 or JAK2, and to a lesser extent TYK2. These kinases phosphorylate IL6ST and LIFR, and the phosphorylated receptors become docking sites for STAT3 and, to a lesser extent, STAT1.
In parallel with the STAT3 pathway, LIF engagement of its receptor activates the MAPK and phosphatidylinositol 3-kinase (PI3K) pathways. JAK1 phosphorylates the p85 subunit of PI3K, leading to activation of AKT. LIF also induces tyrosine phosphorylation of PTPN11, which associates with the IL6ST-LIFR complex and recruits p85, promoting PI3K-AKT activation and GRB2-RAS-MAPK signalling. PI3K-dependent signalling is required for efficient self-renewal of murine embryonic stem cells, and regulation of ERK activity is important in this response. LIF regulates self-renewal, differentiation and survival of embryonic stem cells and is crucial for embryonic implantation.
The LIF gene encodes a pleiotropic cytokine with roles in several systems. It is involved in inducing haematopoietic differentiation in normal and myeloid leukaemia cells, and in neuronal cell differentiation. It also regulates mesenchymal to epithelial conversion during kidney development and may contribute to immune tolerance at the maternal-foetal interface. Alternatively spliced transcript variants encoding multiple isoforms have been observed. LIF belongs to the LIF/OSM family and is classed by HGNC among the interleukin 6 type cytokine family of receptor ligands; the protein was originally named leukaemia inhibitory factor, with CDF, DIA and HILDA as alternative symbols. Mouse and rat each have a Lif ortholog.
LIF regulates self-renewal, differentiation and survival of embryonic stem cells, making it central to studies of pluripotency maintenance.
LIF engagement of LIFR and IL6ST activates JAK1, JAK2 and TYK2, then STAT3 and STAT1, providing a model for gp130-family signalling.
LIF is crucial for embryonic implantation and may contribute to immune tolerance at the maternal-foetal interface.
LIF induces haematopoietic differentiation in normal and myeloid leukaemia cells, as well as neuronal cell differentiation.
LIF is a secreted cytokine that binds the LIFR-IL6ST (gp130) receptor complex and activates JAK kinases, STAT3, MAPK and PI3K-AKT signalling. It regulates embryonic stem cell self-renewal, differentiation and survival, and is crucial for embryonic implantation.
LIF stands for leukaemia inhibitory factor, and the HGNC name is LIF interleukin 6 family cytokine. Aliases include CDF, DIA and HILDA. NCBI Gene notes that alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.
Mouse and rat both have a Lif ortholog, and murine embryonic stem cells are a well-described system for LIF signalling through PI3K and ERK. Check the datasheet of any product for its validated reactivity.
Receptor subunits, other IL-6 family cytokines and downstream signalling proteins connected with LIF biology.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P15018; product specifications from Assay Genie datasheets.