Foltz I N, Schrader J W
The Biomedical Research Centre, The University of British Columbia, Vancouver, Canada.
Blood. 1997 May 1;89(9):3092-6.
The stress-activated protein/c-Jun N-terminal kinases (SAPK/JNK) have been shown to be activated by pro-inflammatory cytokines, as well as physical and chemical stresses. We now show that a variety of hematopoietic growth factors, including Steel locus factor (SLF), granulocyte-macrophage 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 factors activated both 46- and 55-kD isoforms of both SAPK gamma and SAPK alpha. Furthermore, we demonstrate that SAPK activation correlated with the phosphorylation of SAPK/ERK kinase-1 (SEK1) after treatment with SLF or GM-CSF. Interestingly, IL-4, a cytokine with distinctive and important effects on the immune system, was the exception among the hematopoietic growth factors we examined in failing to induce activation of SAPK gamma, SAPK alpha, or SEK1. These findings show that activation of SAPK is involved, not only in responses to stresses, but also in signaling by growth factors that regulate the normal development and function of cells of the immune system.
应激激活蛋白/c-Jun氨基末端激酶（SAPK/JNK）已被证明可被促炎细胞因子以及物理和化学应激激活。我们现在表明，多种造血生长因子，包括Steel位点因子（SLF）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）和白细胞介素-3（IL-3），所有这些因子都能促进各种造血细胞谱系的生长和存活，它们在依赖因子的细胞系MC/9中激活应激激活蛋白激酶。这些造血生长因子激活了SAPKγ和SAPKα的46-kD和55-kD两种亚型。此外，我们证明在用SLF或GM-CSF处理后，SAPK激活与SAPK/ERK激酶-1（SEK1）的磷酸化相关。有趣的是，IL-4是一种对免疫系统有独特且重要作用的细胞因子，在我们检测的造血生长因子中是个例外，它未能诱导SAPKγ、SAPKα或SEK1的激活。这些发现表明，SAPK的激活不仅参与对应激的反应中，还参与调节免疫系统细胞正常发育和功能的生长因子的信号传导。
