| First Author | Zhuang H | Year | 1994 |
| Journal | J Biol Chem | Volume | 269 |
| Issue | 34 | Pages | 21411-4 |
| PubMed ID | 8063772 | Mgi Jnum | J:19924 |
| Mgi Id | MGI:68043 | Doi | 10.1016/s0021-9258(17)31818-5 |
| Citation | Zhuang H, et al. (1994) Inhibition of erythropoietin-induced mitogenesis by a kinase-deficient form of Jak2. J Biol Chem 269(34):21411-4 |
| abstractText | Receptors for a variety of hematopoietins, interferons alpha/beta and gamma, and growth hormone have recently been shown to mediate rapid, ligand-dependent activation of the Janus-type cytosolic protein-tyrosine kinases Jak1, Jak2, and/or tyk-2. This finding extends relatedness among class I and II cytokine receptors to a functional context and provides an initially satisfying mechanistic analogy to protein-tyrosine kinase-encoding receptors of the epidermal growth factor/platelet-derived growth factor/insulin family. Through the construction and expression of a kinase-deficient form of Jak2 (JK2 delta VIII) in interleukin-3 (IL-3)/erythropoietin (Epo)-dependent DAER cells, we have tested whether activation of Jak2 is required for induced mitogenesis via these class I cytokine receptors. Ectopic expression of JK2 delta VIII inhibited Epo- and IL-3-induced activation of endogenous wild-type Jak2, transiently attenuated IL-3-dependent growth, and essentially abrogated Epo-induced proliferation in this model system. These dominant-negative effects provide the first direct experimental evidence for an essential role for Janus kinase activation in mitogenesis and suggest that distinct effectors may mediate IL-3-induced versus Epo-induced pathways. |
