Halfter H, Friedrich M, Postert C, Ringelstein E B, Stögbauer F
Clinic of Neurology, Westf. Wilhelms-Universität Münster, Germany.
Mol Cell Biol Res Commun. 1999 May;1(2):109-16. doi: 10.1006/mcbr.1999.0117.
Oncostatin M (OSM) is a cytokine of the IL-6 family that modulates the growth of various cell types, at least in vitro. We have recently described that OSM inhibits growth and changes cell morphology of human glioma cell lines. Although leukemia inhibitory factor (LIF) receptor components are also expressed by these cells, the response to LIF was significantly weaker compared to OSM. We have therefore analyzed the signal transduction pathways induced by these cytokines. While OSM induces a number of strong tyrosine phosphorylations, including Janus tyrosine kinases (Jak) and the signal transducer and activator of transcription (Stat) proteins, LIF induces only minor tyrosine phosphorylation of Tyk2 and Stat3. Specific activation of the tyrosine phosphatase SHP-2 as well as the mitogen-activated kinase 2 (MAPK2) was found in glioma cells upon OSM treatment. MAPK2 turns out to be a crucial mediator of the OSM effect in glioma cells since inhibition of MAPK activity by the Mek1 inhibitor PD98059 blocks the OSM-induced inhibition of DNA synthesis by about 70%.
抑瘤素M（OSM）是白细胞介素-6家族的一种细胞因子，至少在体外可调节多种细胞类型的生长。我们最近报道，OSM可抑制人胶质瘤细胞系的生长并改变其细胞形态。尽管这些细胞也表达白血病抑制因子（LIF）受体成分，但与OSM相比，它们对LIF的反应明显较弱。因此，我们分析了这些细胞因子诱导的信号转导途径。OSM可诱导包括Janus酪氨酸激酶（Jak）和信号转导及转录激活因子（Stat）蛋白在内的多种强烈的酪氨酸磷酸化，而LIF仅诱导Tyk2和Stat3的轻微酪氨酸磷酸化。在胶质瘤细胞中，OSM处理后可发现酪氨酸磷酸酶SHP-2以及丝裂原活化激酶2（MAPK2）的特异性激活。MAPK2是OSM在胶质瘤细胞中发挥作用的关键介质，因为Mek1抑制剂PD98059抑制MAPK活性可使OSM诱导的DNA合成抑制约70%。
