Calcium as a mediator between erythropoietin and protein tyrosine phosphatase 1B

CALLERO MARIANA; VOTA DAIANA; CHAMORRO M EUGENIA; WENKER SHIRLEY; VITTORI DANIELA; NESSE ALCIRA

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS

ELSEVIER SCIENCE INC

Año: 2011 vol. 505 p. 242 - 249

0003-9861

Erythropoietin (Epo) is crucial for promoting the survival, proliferation, and differentiation of mammalianerythroid progenitors. The central role played by tyrosine phosphorylation of erythropoietin receptor(EpoR) in Epo-cell activation has focused attention on protein tyrosine phosphatases (PTPs) as candidatesimplicated in the pathogenesis of the resistance to therapy with human recombinant Epo. Prototypicmember of the PTP family is PTP1B, which has been implicated in the regulation of EpoR signaling pathways.In previous reports we have shown that PTP1B is reciprocally modulated by Epo in undifferentiatedUT-7 cell line. However, no information is available with respect to the modulation of this phosphatase innon-Epo depending cells or at late stages of erythroid differentiation. In order to investigate these issueswe induced UT-7 cells to differentiate and studied their PTP1B expression pattern. Simultaneous observationswere performed in TF-1 cells which can be cultured either with GM-CSF, IL-3 or Epo. We foundthat Epo induced PTP1B cleaveage in TF-1 and differentiated UT-7 cells. This pattern of PTP1B modulationmay be due to an increased TRPC3/TRPC6 expression ratio which could explain the larger and sustainedcalcium response to Epo and calpain activation in Epo treated TF-1 and differentiated UT-7 cells.