Jun N-terminal kinase promotes proliferation of immature erythroid cells and erythropoietin-dependent cell lines.

Abstract:

:Erythropoietin (EPO) is the hormone necessary for development of erythrocytes from immature erythroid cells. EPO activates Jun N-terminal kinase (JNK), a member of the mitogen-activated protein kinase (MAPK) family in the EPO-dependent murine erythroid HCD57 cells. Therefore, we tested if JNK activity supported proliferation and/or survival of these cells. Treatment with the JNK inhibitor SP600125 inhibited JNK activity and EPO-dependent proliferation of HCD57 cells and the human EPO-dependent cell lines TF-1 and UT7-EPO. SP600125 also increased the fraction of cells in G2/M. Introduction of a dominant-negative form of JNK1 inhibited EPO-dependent proliferation in HCD57 cells but did not increase the fraction of cells in G2/M. Constitutive JNK activity was observed in primary murine erythroid progenitors. Treatment of primary mouse bone marrow cells with the SP600125 inhibitor reduced the number of erythroid burst-forming units (BFU-e's) but not the more differentiated erythroid colony-forming units (CFU-e's), and SP600125 protected the BFU-e's from apoptosis induced by cytosine arabinoside, demonstrating that the SP600125 inhibited proliferation of the BFU-e's. Therefore, JNK activity appears to be an important regulator of proliferation in immature, primary erythroid cells and 3 erythroid cell lines but may not be required for the survival or proliferation of CFU-e's or proerythroblasts.

journal_name

Blood

journal_title

Blood

authors

Jacobs-Helber SM,Sawyer ST

doi

10.1182/blood-2003-05-1754

subject

Has Abstract

pub_date

2004-08-01 00:00:00

pages

696-703

issue

3

eissn

0006-4971

issn

1528-0020

pii

2003-05-1754

journal_volume

104

pub_type

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