Induction of tyrosine phosphorylation of Vav and expression of Pim-1 correlates with Jak2-mediated growth signaling from the erythropoietin receptor

作者: O Miura , Y Miura , N Nakamura , FW Quelle , BA Witthuhn

DOI: 10.1182/BLOOD.V84.12.4135.BLOODJOURNAL84124135

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摘要: The receptor for erythropoietin (Epo) belongs to the cytokine family and lacks a tyrosine kinase domain. However, it has been hypothesized that kinase, Jak2, associates with membrane proximal cytoplasmic region of Epo (EpoR) mediates growth signaling from through phosphorylation cellular substrates. To explore pathways EpoR, we analyzed substrates induced by stimulation in cells expressing various mutant EpoRs. vav proto-oncogene product was found be phosphorylated after wild-type EpoR or truncated receptor, H mutant, retains function. In these cells, also expression serine/threonine Pim-1. did not have any effect on Vav Pim-1 PM4 inactivated point mutation, Trp282 Arg, region, which abrogates interaction Jak2. On other hand, both were observed constitutively is activated Arg 129 Cys, extracellular Jak2 this confirms crucial role EpoR. Taken together, observations suggest may play important roles

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