Erythropoietin (EPO) is the principal hormone regulating the proliferation of erythroid precursors and their differentiation into erythrocytes. Binding of ligand to the cell-surface EPO-R (EPO receptor) induces dimerization and JAK2 (Janus kinase 2)-mediated tyrosine phosphorylation of the receptor. Less than 1% of the EPO-Rs are displayed on the cell surface; most of the receptor molecules are retained in intracellular compartments, including the ER (endoplasmic reticulum). Using pervanadate (PV) as a potent tool to inhibit cellular PTPs (protein tyrosine phosphatases), we demonstrated previously the accumulation of mature (endoglycosidase H-resistant) tyrosine-phosphorylated EPO-R [Cohen, Altaratz, Zick, Klingmuller and Neumann (1997) Biochem. J. 327, 391–397]. In the present study, we investigated the participation of the ER-associated PTP1B in the dephosphorylation of intracellular EPO-R. We demonstrate tyrosine phosphorylation of EPO-R in BOSC-23T cells co-expressing EPO-R and the ‘substrate-trapping’ mutant form of PTP1B, PTP1B D181A (referred to as PTP1BD). In vivo interaction between EPO-R and PTP1B suggested that PTP1B dephosphorylates the EPO-R intracellularly. Endoglycosidase H resistance of tyrosine-phosphorylated EPO-R in cells expressing PTP1BD suggested that mature EPO-R is dephosphorylated by PTP1B. Stimulation with EPO of cells co-expressing EPO-R and either PTP1BD or PTP1B resulted in an increase or decrease respectively in phosphotyrosine EPO-R. We thus suggest that PTP1B dephosphorylates EPO-stimulated EPO-R and participates in the down-regulation cascade of EPO-mediated signal transduction.
Skip Nav Destination
Article navigation
January 2004
- PDF Icon PDF LinkFront Matter
Research Article|
January 15 2004
Protein tyrosine phosphatase 1B participates in the down-regulation of erythropoietin receptor signalling
Jacob COHEN;
Jacob COHEN
1
*Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel
Search for other works by this author on:
Liat OREN-YOUNG;
Liat OREN-YOUNG
1
*Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel
Search for other works by this author on:
Ursula KLINGMULLER;
Ursula KLINGMULLER
2
†Hans-Spemann Laboratory, Max Planck Institut für Immunobiologie, Stübeweg 51, Freiburg D-79108, Germany
Search for other works by this author on:
Drorit NEUMANN
Drorit NEUMANN
3
*Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel
3To whom correspondence should be addressed (e-mail histo6@post.tau.ac.il).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
September 17 2003
Accepted:
October 06 2003
Accepted Manuscript online:
October 06 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2004
2004
Biochem J (2004) 377 (2): 517–524.
Article history
Received:
September 17 2003
Accepted:
October 06 2003
Accepted Manuscript online:
October 06 2003
Citation
Jacob COHEN, Liat OREN-YOUNG, Ursula KLINGMULLER, Drorit NEUMANN; Protein tyrosine phosphatase 1B participates in the down-regulation of erythropoietin receptor signalling. Biochem J 15 January 2004; 377 (2): 517–524. doi: https://doi.org/10.1042/bj20031420
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.