| First Author | Kamata T | Year | 2004 |
| Journal | Blood | Volume | 103 |
| Issue | 7 | Pages | 2568-70 |
| PubMed ID | 14576068 | Mgi Jnum | J:89053 |
| Mgi Id | MGI:3038021 | Doi | 10.1182/blood-2003-06-1803 |
| Citation | Kamata T, et al. (2004) Raf-1 is not required for megakaryocytopoiesis or TPO-induced ERK phosphorylation. Blood 103(7):2568-70 |
| abstractText | Thrombopoietin stimulates extracellular signal-related kinase 1/2 (ERK1/2) phosphorylation in megakaryocytes, and the classic mitogen-activated protein (MAP) kinase (Raf/mitogen-induced extracellular kinase [MEK]/ERK) pathway has been implicated directly and indirectly to play a critical role in megakaryocytopoiesis. However, the involvement of specific Raf family members in megakaryocytopoiesis is unknown. raf-1(-/-) mice were therefore used to directly determine the role of Raf-1 in megakaryocytopoiesis. Surprisingly, raf-1(-/-) mice have a modestly higher platelet count than their raf-1(+/+) littermates. Nonetheless, the absence of Raf-1 does not alter thrombopoietin-induced expansion of primary megakaryocyte-lineage cells, the development of apoptotic megakaryocytes in the presence or absence of thrombopoietin, or the development of megakaryocyte DNA ploidy distribution. Moreover, raf-1(-/-) megakaryocytes do not have a compensatory increase in A-Raf or B-Raf expression, and thrombopoietin-induced ERK1/2 phosphorylation is similar in raf-1(-/-) and raf-1(+/+) megakaryocytes. These unexpected findings demonstrate that Raf-1 is dispensable for megakaryocytopoiesis, and for thrombopoietin-induced ERK1/2 activation in primary megakaryocyte-lineage cells. |
