Modulation of Protein Tyrosine Phosphatase 1B by Erythropoietin in UT-7 Cell line

CALLERO, MARIANA; PEREZ, GLADYS; PREGI, NICOLAS; VITTORI, DANIELA; NESSE, ALCIRA

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY : INTERNATIONAL JOURNAL OF EXPERIMENTAL CELLULAR PHYSIOLOGY, BIOCHEMISTRY, AND PHARMACOLOGY.

Karger

Lugar: Basel, Suiza; Año: 2007 vol. 20 p. 319 - 328

1015-8987

Since the reversible phosphorylation of tyrosyl residues is a critical event in cellular signaling pathways activated by erythropoietin (Epo), attention has been focused on protein tyrosine phosphatases (PTPs) and their coordinated action with protein tyrosine kinases. The prototypic member of the PTP family is PTP1B, a widely expressed non-receptor PTP located both in cytosol and intracellular membranes via its hydrophobic C-terminal targeting sequence. PTP1B has been implicated in the regulation of signaling pathways involving tyrosine phosphorylation induced by growth factors, cytokines and hormones, such as the downregulation of erythropoietin and insulin receptors. However, little is known about which factor modulates the enzyme activity. In the present investigation, the effect of Epo on PTP1B expression in the UT-7 Epo-dependent cell line was studied. PTP1B expression was analyzed under different conditions by Real-Tme PCR and Western blot while the PTP1B phosphatase activity was determined by a p-nitrophenylphosphate hydrolysis assay. Epo rapidly induced an increased expression of PTP1B which was associated with higher PTP1B Tyr phosphorylation and phosphatase activity. Besides, Epo-stimulation involving Janus Kinase 2 (Jak2) and Phosphatidylinositol-3 kinase (PI3K) appeared to be necessary for the induction of PTP1B. The results suggest that besides modulating Epo/Epo receptor signaling, PTP1B undergoes a feedback regulation by Epo.