Target type: molecularfunction
Combining with leukemia inhibitory factor (LIF) and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity. [GOC:bf, GOC:mah, GOC:signaling]
Leukemia inhibitory factor receptor (LIFR) activity is a critical component of the cytokine signaling pathway, specifically for LIF and other related cytokines. It acts as a transmembrane receptor that binds to LIF, initiating a cascade of intracellular events leading to cellular responses. Here's a detailed breakdown of its molecular function:
1. **Ligand Binding:** LIFR, along with its co-receptor gp130, forms a heterodimer complex. The binding of LIF to this complex triggers a conformational change in the receptor.
2. **Signal Transduction:** This conformational change activates the intracellular tyrosine kinase domains of gp130. The activated kinases phosphorylate tyrosine residues on the cytoplasmic tails of LIFR and gp130.
3. **JAK-STAT Pathway Activation:** Phosphorylated tyrosine residues serve as docking sites for the Janus kinase (JAK) family of tyrosine kinases. These kinases further phosphorylate each other, leading to their activation. Activated JAKs then phosphorylate signal transducer and activator of transcription (STAT) proteins.
4. **STAT Dimerization and Nuclear Translocation:** Phosphorylated STATs dimerize and translocate to the nucleus.
5. **Transcriptional Regulation:** In the nucleus, STAT dimers bind to specific DNA sequences, known as STAT response elements, in the promoter regions of target genes. This binding activates transcription of target genes.
6. **Cellular Responses:** LIFR-mediated signaling leads to a wide range of cellular responses, including:
* Cell proliferation and differentiation
* Immune regulation
* Neuroprotection
* Embryonic development
* Tissue regeneration
LIFR activity is crucial for various developmental processes, immune system regulation, and maintaining tissue homeostasis. Dysregulation of LIFR signaling has been implicated in various disease conditions, including cancer, inflammation, and neurodegenerative disorders.'
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Protein | Definition | Taxonomy |
---|---|---|
Interleukin-6 receptor subunit beta | An interleukin-6 receptor subunit beta that is encoded in the genome of human. [PRO:WCB, UniProtKB:P40189] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
madindoline a | madindoline A: inhibits interleukin-6; isolated from Streptomyces; structure in first source | ||
lmt-28 | LMT-28: an interleukin-6 inhibitor that binds gp130; structure in first source |