IQUIBICEN   23947
INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CIENCIAS EXACTAS Y NATURALES
Unidad Ejecutora - UE
artículos
Título:
Protein tyrosine phosphatase 1B (PTP1B) is involved in the defective erythropoietic function of carbamylated erythropoietin
Autor/es:
CHAMORRO, ME; MALTANERI, R; VITTORI, D; NESSE, A
Revista:
INTERNATIONAL JOURNAL OF BIOCHEMISTRY AND CELLULAR BIOLOGY
Editorial:
PERGAMON-ELSEVIER SCIENCE LTD
Referencias:
Año: 2015 p. 63 - 71
ISSN:
1357-2725
Resumen:
It is now recognized that the carbamylation of erythropoietin renders this protein unable to act as an erythopoietic growth factor, while it retains its ability to protect neuronal cells from damage. In a previous work, we reported for the first time the inability of cEpo to completely activate proliferation signaling pathways. In order to investigate this point further, we used the UT-7 cell line as an erythroid model. Immunoprecipitation, Western blotting, flow cytometry and confocal microscopy were employed in this work. Although Jak2 phosphorylation was induced by Epo and cEpo, activation by the latter rapidly disappeared while Epo showed a more prolonged effect. Similar results were observed for the time course of Akt and ERK1/2 phosphorylation. FOXO3a phosphorylation increased in a time-dependent manner due to Epo activation, while rapidly decreased in the presence of cEpo. These findings are in line with significantly higher protein levels and enzyme activity of PTP1B induced by cEpo in comparison to Epo. Besides, PTP1B colocalized with EpoR and commonR, component subunits of the heteroreceptor used by cEpo. Furthermore, specific PTP1B inhibition by CinnGel 2M and non-specific inhibition of phosphatase activity by o-vanadate partially restored the ability of cEpo to induce proliferation of UT-7 cells. In conclusion, we suggest that the catalytic activity of PTP1B and probably other phosphatases appears necessary to deprive cEpo of erythropoietic function. This is the first report showing a tight relationship between the dephosphorylation rate of signaling pathways and the lack of proliferative function of carbamylated erythropoietin.