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Different levels of p38 MAP kinase activity mediate distinct biological effects in primary human erythroid progenitors
Author(s) -
Somervaille Tim C. P.,
Linch David C.,
Khwaja Asim
Publication year - 2003
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2003.04204.x
Subject(s) - mapk/erk pathway , p38 mitogen activated protein kinases , microbiology and biotechnology , biology , apoptosis , erythropoietin , progenitor cell , protein kinase a , kinase , cell culture , stem cell , endocrinology , biochemistry , genetics
Summary. There have been conflicting reports regarding the role of p38 mitogen‐activated protein kinase (MAPK) in the regulation of differentiation, proliferation and apoptosis in erythroid cell lines. We have, therefore, examined the functions of this kinase in primary human erythroid progenitors. Cells in steady‐state culture showed low‐level p38 MAPK activity, which decreased further within 1 h of growth factor withdrawal and increased over a limited range within minutes of re‐exposure of cells to erythropoietin or stem cell factor, demonstrating the link between low‐level p38 MAPK activity and the prevailing growth factor milieu. Use of the p38 MAPK‐specific inhibitor SB203580 demonstrated that this level of activity was necessary for (1) optimal proliferation, (2) erythroid burst‐forming unit migration and (3) full upregulation of E‐cadherin and CD36 expression, but not haemoglobin A or glycophorin A expression, during human erythroid differentiation. In contrast, cells deprived of growth factors for an 8‐h period, following a transient decrease in p38 MAPK activity, demonstrated sustained, substantial and caspase‐independent increases in p38 MAPK activity, and its blockade using SB203580 reduced the proportion of erythroblasts undergoing apoptosis by 40 ± 7%, demonstrating a role for p38 MAPK in apoptosis induction in human erythroblasts. Thus, in primary human erythroblasts, different environmental conditions induce different levels of p38 MAPK activity, which have distinct functions.