Activation of p38 MAP kinase pathway by erythropoietin and interleukin-3

• Published in: Blood Vol. 90; no. 3; pp. 929 - 934
• Main Authors: NAGATA, Y, MORIGUCHI, T, NISHIDA, E, TODOKORO, K
• Format: Journal Article
• Language: English
• Published: Washington, DC The Americain Society of Hematology 01.08.1997
• Subjects: Analytical, structural and metabolic biochemistry; Animals; Biological and medical sciences; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; Cell Line; Enzyme Activation - drug effects; Enzymes and enzyme inhibitors; Erythropoietin - pharmacology; Fundamental and applied biological sciences. Psychology; Hematopoiesis; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - enzymology; Inflammation; Interleukin-3 - pharmacology; Mice; Mitogen-Activated Protein Kinases; p38 Mitogen-Activated Protein Kinases; Phosphorylation - drug effects; Protein Processing, Post-Translational - drug effects; Signal Transduction - drug effects; Stress, Physiological - metabolism; Transferases; Human; Signal transduction; Erythropoietin; Enzyme; Interleukin 3; Protein kinase; Transferases; Cytokine; Activation; Mitogen; Glycoprotein hormone
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.v90.3.929

Activation of p38 MAP kinase (p38) as well as JNK/SAPK has been described as being induced by a variety of environmental stresses such as osmotic shock, ultraviolet radiation, and heat shock, or the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1 (IL-1). We found that the hematopoietic cytokines erythropoietin (Epo) and IL-3, which regulate growth and differentiation of erythroids and hematopoietic progenitors, respectively, also activate a p38 cascade. Immunoblot analyses and in vitro kinase assay clearly showed that Epo and IL-3 rapidly and transiently phosphorylated and activated p38 in Epo- or IL-3-dependent mouse hematopoietic progenitor cells. p38 can generally be activated by the upstream kinase MKK3 or MKK6. However, in vitro kinase assays in the immunoprecipitates with anti-MKK6 antibody and anti-phosphorylated MKK3/MKK6 antibody showed that activation of neither MKK3 nor MKK6 was detected after Epo or IL-3 stimulation, while osmotic shock clearly induced activation of both MKK3/MKK6 and p38. Together with previous observations, these results suggest that both p38 and JNK cascades play an important role not only in stress and proinflammatory cytokine responses but also in hematopoietic cytokine actions.