Fyn kinase is a novel modulator of erythropoietin signaling and stress erythropoiesis

Elisabetta Beneduce, Alessandro Matte, Luigia De Falco, Serge Mbiandjeu, Deborah Chiabrando, Emanuela Tolosano, Enrica Federti, Sara Petrillo, Narla Mohandas, Angela Siciliano, Wilson Babu, Vijay Menon, Saghi Ghaffari, Achille Iolascon, Lucia De Franceschi

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)10-20
Number of pages11
JournalAmerican Journal of Hematology
Volume94
Issue number1
DOIs
StatePublished - Jan 2019

Fingerprint

Dive into the research topics of 'Fyn kinase is a novel modulator of erythropoietin signaling and stress erythropoiesis'. Together they form a unique fingerprint.

Cite this