The α subunit of the granulocyte-macrophage colony-stimulating factor receptor interacts with c-Kit and inhibits c-Kit signaling Journal Article
| Authors: | Chen, J.; Cárcamo, J. M.; Golde, D. W. |
| Article Title: | The α subunit of the granulocyte-macrophage colony-stimulating factor receptor interacts with c-Kit and inhibits c-Kit signaling |
| Abstract: | 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 α (αGMR)and β (βGMR) 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 αGMR directly interacts with c-Kit and that the interaction is mediated by the cytoplasmic domains. Furthermore, αGMR inhibited c-Kit auto-phosphorylation induced by the ligand stem cell factor. Consistent with the inhibitory effect, the expression of αGMR was suppressed in cells whose viability was dependent on c-Kit signaling. In contrast, the alternatively spliced α2 isoform of the αGMR could not inhibit c-Kit signaling, providing a rationale for the existence of the α2 isoform. Our results suggest that in addition to having the commonly appreciated roles in cytokine signal transduction, thereceptors αGMR and c-Kit could interact to coordinate their signal initiation. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc. |
| Keywords: | signal transduction; human cell; cell viability; stem cell factor; stem cell factor receptor; proto-oncogene proteins c-kit; cell line; protein binding; transfection; protein tyrosine kinase; autophosphorylation; phosphorylation; cell membrane; erythroid cell; hematopoiesis; protein subunits; host resistance; biochemistry; alpha chain; protein isoforms; cells; microorganisms; enzyme immobilization; cytokine receptors; signal initiation; granulocyte macrophage colony stimulating factor receptor; receptors, granulocyte-macrophage colony-stimulating factor |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 281 |
| Issue: | 31 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2006-08-04 |
| Start Page: | 22421 |
| End Page: | 22426 |
| Language: | English |
| DOI: | 10.1074/jbc.M604644200 |
| PUBMED: | 16760463 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 6" - "Export Date: 4 June 2012" - "CODEN: JBCHA" - "Source: Scopus" |
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