LIFR

Leukemia inhibitory factor receptor (LIFR), also known as the LIF receptor, is a transmembrane glycoprotein that constitutes part of the type I cytokine receptor family. The human LIFR gene encodes the receptor subunit that together with gp130 (IL6ST) forms the functional receptor for leukemia inhibitory factor and related cytokines. The receptor complex is activated when a LIF-family cytokine binds to LIFR, recruiting gp130 and initiating intracellular signaling.

Signaling: The LIFR-gp130 receptor activates JAK kinases, leading to phosphorylation and activation of STAT transcription factors (especially STAT3), and also triggers MAPK/ERK and PI3K-AKT pathways. This signaling regulates gene expression and cellular responses such as survival, differentiation, and proliferation. LIFR is broadly expressed in many tissues, including the nervous system, bone, muscle, liver, and immune cells.

Biological roles: In development and homeostasis, LIFR signaling supports neural development and maintenance, hematopoiesis, bone remodeling, muscle regeneration, and liver regeneration after injury. It also participates in inflammatory responses and tissue protection in stress conditions. The activity of LIFR is modulated by the availability of gp130 and other LIF-family cytokines, such as CNTF and oncostatin M, which use LIFR as a co-receptor.

Clinical significance: Germline mutations in LIFR cause Stuve-Wiedemann syndrome, a severe skeletal dysplasia with hypotonia and respiratory complications. Other LIFR-related disorders include congenital myopathies in some cases. In research, altered LIFR signaling has been explored in cancer and inflammatory diseases, and LIFR is sometimes discussed as a potential metastasis suppressor in certain cancers.