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Signaling Functions of the Tyrosine Residues in the βc Chain of the Granulocyte-Macrophage Colony-Stimulating Factor Receptor
| Content Provider | Scilit |
|---|---|
| Author | Okuda, Keiko Smith, Lorie Griffin, James D. Foster, Rosemary |
| Copyright Year | 1997 |
| Description | The granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor (GMR) is a heterodimeric receptor expressed by myeloid lineage cells. Binding of GM-CSF activates at least one receptor-associated tyrosine kinase, JAK2, and rapidly induces tyrosine phosphorylation of the GMR βc-chain (GMRβ), but not the GMR α-chain (GMRα). To examine the role of GMRβ tyrosine phosphorylaiton, each of the 8 tyrosine residues in the cytoplasmic domain of the human GMRβ was mutated to phenylalanine (GMRβ-F8), and this mutant receptor was expressed with wild-type GMRα in the interleukin-3–dependent murine hematopoietic cell line, Ba/F3. GM-CSF induced tyrosine phosphorylation of multiple cellular proteins in cells expressing GMRβ-F8 , including JAK2 and STAT5. However, GM-CSF–induced tyrosine phosphorylation of both SHP2 and SHC was reduced or absent compared with wild-type. Next, a series of 8 receptors were generated, each containing only a single, restored, tyrosine residue. Tyrosine 577 was found to be sufficient to regenerate GM-CSF–dependent phosphorylation of SHC, and any of Y577, Y612, or Y695 was sufficient to regenerate GM-CSF–inducible phosphorylation of SHP2. Despite the signaling defect to SHC and SHP2, Ba/F3 cells expressing GMRβ-F8 were still able to proliferate in response to 10 ng/mL of human GM-CSF, although mitogenesis was impaired compared with wild-type GMRβ, and this effect was even more prominent at lower concentrations of GM-CSF (1 ng/mL). Overall, these results indicate that GMRβ tyrosine residues are not necessary for activation of the JAK/STAT pathway or for proliferation, viability, or adhesion signaling in Ba/F3 cells, although tyrosine residues significantly affect the magnitude of the response. However, specific tyrosine residues are needed for activation of SHC and SHP2. |
| Related Links | https://ashpublications.org/blood/article-pdf/90/12/4759/226937/4759.pdf |
| Ending Page | 4766 |
| Page Count | 8 |
| Starting Page | 4759 |
| DOI | 10.1182/blood.v90.12.4759.4759_4759_4766 |
| Journal | Blood |
| Issue Number | 12 |
| Volume Number | 90 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 1997-12-15 |
| Access Restriction | Open |
| Subject Keyword | Immunology Phosphorylation Gm Csf Tyrosine Residues Csfâ Journal: Blood (Vol- 120, Issue- 12) |
| Content Type | Text |
| Resource Type | Article |
