| First Author | Beneduce E | Year | 2019 |
| Journal | Am J Hematol | Volume | 94 |
| Issue | 1 | Pages | 10-20 |
| PubMed ID | 30252956 | Mgi Jnum | J:295498 |
| Mgi Id | MGI:6453886 | Doi | 10.1002/ajh.25295 |
| Citation | Beneduce E, et al. (2019) Fyn kinase is a novel modulator of erythropoietin signaling and stress erythropoiesis. Am J Hematol 94(1):10-20 |
| abstractText | The signaling cascade induced by the interaction of erythropoietin (EPO) with its receptor (EPO-R) is a key event of erythropoiesis. We present here data indicating that Fyn, a Src-family-kinase, participates in the EPO signaling-pathway, since Fyn(-/-) mice exhibit reduced Tyr-phosphorylation of EPO-R and decreased STAT5-activity. The importance of Fyn in erythropoiesis is also supported by the blunted responsiveness of Fyn(-/-) mice to stress erythropoiesis. Fyn(-/-) mouse erythroblasts adapt to reactive oxygen species (ROS) by activating the redox-related-transcription-factor Nrf2. However, since Fyn is a physiologic repressor of Nrf2, absence of Fyn resulted in persistent-activation of Nrf2 and accumulation of nonfunctional proteins. ROS-induced over-activation of Jak2-Akt-mTOR-pathway and repression of autophagy with perturbation of lysosomal-clearance were also noted. Treatment with Rapamycin, a mTOR-inhibitor and autophagy activator, ameliorates Fyn(-/-) mouse baseline erythropoiesis and erythropoietic response to oxidative-stress. These findings identify a novel multimodal action of Fyn in the regulation of normal and stress erythropoiesis. |
