| First Author | Yu WM | Year | 2003 |
| Journal | Oncogene | Volume | 22 |
| Issue | 38 | Pages | 5995-6004 |
| PubMed ID | 12955078 | Mgi Jnum | J:85530 |
| Mgi Id | MGI:2675565 | Doi | 10.1038/sj.onc.1206846 |
| Citation | Yu WM, et al. (2003) Catalytic-dependent and -independent roles of SHP-2 tyrosine phosphatase in interleukin-3 signaling. Oncogene 22(38):5995-6004 |
| abstractText | SHP-2 tyrosine phosphatase is highly expressed in hematopoietic cells, however, the function of SHP-2 in hematopoietic cell signaling is not well understood. Here we focus on the role of SHP-2 phosphatase in the signal transduction of interleukin (IL)-3, a cytokine involved in hematopoietic cell survival, proliferation, and differentiation. We established immortalized SHP-2(-/-) hematopoietic cell pools and showed that IL-3-induced proliferative response was diminished in SHP-2(-/-) cells. Moreover, inhibition of the catalytic activity of SHP-2 in wild-type (WT) bone marrow hematopoietic progenitor cells and Ba/F3 cells by overexpression of catalytically inactive SHP-2 mutant suppressed their differentiative and proliferative responses to IL-3, demonstrating an important positive role for SHP-2 in IL-3 signal transduction. Further biochemical analyses revealed that IL-3-induced Jak/Stat, Erk, and PI3 kinase pathways in SHP-2(-/-) cells were impaired and reintroduction of WT SHP-2 into mutant cells partially restored IL-3 signaling. Interestingly, in catalytically inactive SHP-2-overexpressing Ba/F3 cells, although IL-3-induced activation of Jak2 and Erk kinases was reduced and shortened, PI3 kinase activation remained unaltered. Taken together, these results suggest that SHP-2 tyrosine phosphatase plays multiple roles in IL-3 signal transduction, functioning in both catalytic-dependent and -independent manners in the Jak/Stat, Erk, and PI3 kinase pathways. |
