oncostatin-M-mediated signaling pathway

Definition

Target type: biologicalprocess

The series of molecular signals initiated by oncostatin-M (OSM) binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. OSM can signal via at least two different receptors (a specific receptor and a LIF receptor) to activate different downstream signal transduction pathways. [GOC:nhn, GOC:signaling, PMID:10579456, PMID:12811586]

Oncostatin M (OSM) is a pleiotropic cytokine that exerts a wide range of biological effects on various cell types. It plays a significant role in inflammation, immunity, and tissue repair. The OSM signaling pathway is initiated by the binding of OSM to its receptor complex, which comprises the OSM receptor beta (OSMRβ) and the glycoprotein 130 (gp130). This binding event triggers a cascade of intracellular signaling events, leading to the activation of downstream effectors that ultimately modify cellular functions.

The OSM receptor complex is a heterotetrameric structure composed of two OSMRβ subunits and two gp130 subunits. OSMRβ serves as the specific receptor for OSM, while gp130 is a shared receptor subunit for a variety of cytokines, including interleukin-6 (IL-6), leukemia inhibitory factor (LIF), and ciliary neurotrophic factor (CNTF). The association of OSM with the OSMRβ/gp130 complex results in the dimerization of the receptor complex, leading to the activation of its associated Janus kinase (JAK) family members, primarily JAK1 and JAK2.

Once activated, JAK1 and JAK2 phosphorylate tyrosine residues within the cytoplasmic domains of OSMRβ and gp130. These phosphorylated tyrosines serve as docking sites for the recruitment of signal transducer and activator of transcription (STAT) proteins, specifically STAT1, STAT3, and STAT5. The STAT proteins bind to the phosphorylated tyrosines and are themselves phosphorylated by the JAK kinases.

Phosphorylated STAT proteins dimerize and translocate from the cytoplasm to the nucleus, where they act as transcription factors, binding to specific DNA sequences known as STAT-binding elements (SBE). This binding initiates the transcription of target genes, ultimately leading to the expression of proteins involved in various biological processes, including cell proliferation, differentiation, apoptosis, and immune responses.

The OSM signaling pathway is tightly regulated by a variety of mechanisms, including negative feedback loops and protein-protein interactions. The interplay of these regulatory mechanisms ensures that the signaling pathway is activated only when necessary and that it does not become uncontrolled.

The dysregulation of OSM signaling has been implicated in the pathogenesis of various diseases, including cancer, inflammatory disorders, and autoimmune diseases. For instance, OSM has been shown to promote tumor growth and metastasis in certain cancers. Moreover, elevated levels of OSM have been observed in inflammatory bowel disease and rheumatoid arthritis, suggesting a role for OSM in the pathogenesis of these diseases.

In summary, the OSM signaling pathway is a complex and multifaceted process that plays a critical role in diverse cellular functions. The activation of this pathway involves the binding of OSM to its receptor complex, the phosphorylation of receptor subunits by JAK kinases, the recruitment and phosphorylation of STAT proteins, and the translocation of STAT dimers to the nucleus to activate gene transcription. The dysregulation of OSM signaling is implicated in the pathogenesis of various diseases, highlighting the importance of understanding and manipulating this pathway for therapeutic purposes.'
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Proteins (1)

Compounds (2)