Reprogramming Cell-Signaling By Delivering the Catalytic Domain of Ptpgr Ameliorates Anemia of β-Thalassemia

β-thalassemia (β-thal) is one of the most common monogenic disorders worldwide, characterized by ineffective erythropoiesis leading to a chronic, debilitating anemia associated with high morbidity and mortality. Erythroid maturation is a dynamic process tightly regulated by complex signaling mechanisms, only partially described either in normal and diseased erythropoiesis. To investigate this issue, we carried out a high throughput kinome analysis by taking advantage of Kinexus array technology (http://www.kinexus.ca), in sorted erythroid precursors from a mouse model of β-thalassemia (Hbb3th/+) compared to wildtype animals. In β-thal mice, we found differential modulation of many protein kinases. Network computational analysis unveiled common as well as erythroid precursor-specific signaling mechanisms of altered erythrocyte differentiation in beta thalassemia, suggesting a selective perturbation in protein kinase/phosphatase balance in β-thal erythropoiesis.