Related Experiment Videos
Signaling of type II oncostatin M receptor
P Auguste1, C Guillet, M Fourcin
1Laboratoire de Biologie Cellulaire, 4 rue Larrey, CHU Angers, 49033 Angers Cedex, France.
Abstract:
Oncostatin M (OSM) mediates its bioactivities through two different heterodimer receptors. They both involve the gp130-transducing receptor, which dimerizes with either leukemia inhibitory receptor beta or with OSM receptor beta (OSMRbeta) to generate, respectively, type I and type II OSM receptors. Co-precipitation of gp130-associated proteins, flow cytometry, polymerase chain reaction, and tyrosine phosphorylation analyses allowed the characterization of both types of OSM receptors expressed on the surface of different cell lines. It also allowed the detection of a large size protein, p250, that specifically associates to the type II OSM receptor components and that is tyrosine-phosphorylated after the activation peak of the gp130.OSMRbeta heterocomplex. The restricted expression of type I OSM receptor by the JAR choriocarcinoma cell line, and type II receptor by the A375 melanoma cell line, permitted the characterization of their signaling machineries. Both type I and type II OSM receptors activated Jak1, Jak2, and Tyk2 receptor-associated tyrosine kinases. The information is next relayed to the nucleus by the STAT3 transcriptional activator, which is recruited by both types of OSM receptors. In addition, STAT5b was specifically activated through the gp130.OSMRbeta type II heterocomplex. The signaling pathway differences observed between the common type I LIF/OSM receptor and the specific type II OSM receptor might explain some of the bioactivities specifically displayed by OSM.
Insights
Oncostatin M (OSM) uses two receptor types, gp130.LIFRbeta (type I) and gp130.OSMRbeta (type II), to signal. Type II receptors uniquely activate STAT5b, explaining some of OSM's specific biological activities.
Area of Science:
- Cell biology
- Molecular signaling
- Receptor biology
Background:
- Oncostatin M (OSM) is a cytokine with diverse biological functions.
- OSM exerts its effects through heterodimeric receptor complexes involving gp130.
- Two distinct OSM receptor types, type I (gp130/LIFRbeta) and type II (gp130/OSMRbeta), have been proposed.
Purpose of the Study:
- To characterize the distinct signaling pathways of type I and type II OSM receptors.
- To identify unique components or activation patterns associated with each receptor type.
- To elucidate the molecular basis for specific Oncostatin M bioactivities.
Main Methods:
- Co-precipitation assays to identify associated proteins.
- Flow cytometry for receptor expression analysis.
- Polymerase chain reaction (PCR) for gene expression.
- Tyrosine phosphorylation analysis to assess kinase activation.
- Cell line-specific expression studies (JAR and A375 cells).
Main Results:
- Both type I and type II OSM receptors activate Jak1, Jak2, Tyk2, and STAT3.
- A novel protein, p250, specifically associates with the type II OSM receptor and is tyrosine-phosphorylated.
- STAT5b activation is specifically observed through the type II OSM receptor (gp130.OSMRbeta).
- Differential signaling pathways were confirmed between type I and type II OSM receptors.
Conclusions:
- The distinct signaling pathways, particularly STAT5b activation via the type II receptor, contribute to Oncostatin M's specific biological effects.
- The identification of p250 provides a new target for understanding type II OSM receptor function.
- Understanding these receptor-specific pathways is crucial for deciphering OSM's complex roles in physiology and disease.