| First Author | Chen J | Year | 2006 |
| Journal | J Biol Chem | Volume | 281 |
| Issue | 31 | Pages | 22421-6 |
| PubMed ID | 16760463 | Mgi Jnum | J:116468 |
| Mgi Id | MGI:3694332 | Doi | 10.1074/jbc.M604644200 |
| Citation | Chen J, et al. (2006) The alpha subunit of the granulocyte-macrophage colony-stimulating factor receptor interacts with c-Kit and inhibits c-Kit signaling. J Biol Chem 281(31):22421-6 |
| abstractText | The cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) regulates hematopoiesis and the function of mature host defense cells through the GM-CSF receptor (GMR), which is composed of alpha (alphaGMR) and beta (betaGMR) subunits. Stem cell factor is another important hematopoietic cytokine that signals through c-Kit, a receptor tyrosine kinase, and regulates hematopoietic stem cell maintenance and erythroid development. Like other cytokine receptors, GMR and c-Kit are generally deemed as independent adaptor molecules capable of transducing cytokine-specific signals. We found that the alphaGMR directly interacts with c-Kit and that the interaction is mediated by the cytoplasmic domains. Furthermore, alphaGMR inhibited c-Kit auto-phosphorylation induced by the ligand stem cell factor. Consistent with the inhibitory effect, the expression of alphaGMR was suppressed in cells whose viability was dependent on c-Kit signaling. In contrast, the alternatively spliced alpha2 isoform of the alphaGMR could not inhibit c-Kit signaling, providing a rationale for the existence of the alpha2 isoform. Our results suggest that in addition to having the commonly appreciated roles in cytokine signal transduction, the receptors alphaGMR and c-Kit could interact to coordinate their signal initiation. |
