ACTIVATION OF THE STRESS-ACTIVATED PROTEIN-KINASES BY MULTIPLE HEMATOPOIETIC GROWTH-FACTORS WITH THE EXCEPTION OF INTERLEUKIN-4

The stress-activated protein/c-Jun N-terminal kinases (SAPK/JNK) have been shown to be activated by pro-inflammatory cytokines, as well as p hysical and chemical stresses. We now show that a variety of hematopoi etic growth factors, including Steel locus factor (SLF), granulocyte-m acrophage colony-stimulating factor (GM-CSF), and interleukin-3 (IL-3) , all of which promote the growth and survival of various lineages of hematopoietic cells, activate the stress-activated protein kinases in the factor-dependent cell line MC/9. These hematopoietic growth factor s activated both 46- and 55-kD isoforms of both SAPK gamma and SAPK al pha. Furthermore, we demonstrate that SAPK activation correlated with the phosphorylation of SAPK/ERK kinase-l (SEK1) after treatment with S LF or GM-CSF. interestingly, IL-4, a cytokine with distinctive and imp ortant effects on the immune system, was the exception among the hemat opoietic growth factors we examined in failing to induce activation of SAPK gamma SAPK alpha, or SEK1, These findings show that activation o f SAPK is involved, not only in responses to stresses, but also in sig naling by growth factors that regulate the normal development and func tion of cells of the immune system. (C) 1997 by The American Society o f Hematology.