Kumar G, Gupta S, Wang S, Nel A E
Department of Medicine, UCLA School of Medicine 90024.
J Immunol. 1994 Nov 15;153(10):4436-47.
We have previously shown that the IL-6R in a growth-responsive B cell line, AF10, induces activation of mitogen-activated protein (MAP) kinase. Here we demonstrate the activation of Raf-1 and MEK-1, which act as a MAP kinase kinase kinase and a MAP kinase kinase, respectively, in the MAP kinase cascade induced by IL-6 in AF10 cells. IL-6 also induced tyrosine phosphorylation of the signaling transducing subunit of the IL-6R in AF10 cells, along with tyrosine phosphorylation of the gp130-associated tyrosine protein kinase JAK1 and the adaptor molecule p52shc. Although induction of tyrosine phosphorylation and activation of MAP kinase by IL-6 in a differentiation-responsive B cell line, SKW 6.4, were below the limits of detection, the phorbol ester PMA did activate Raf-1, MEK-1, and MAP kinase without inducing the phosphorylation of gp130, JAKs, or p52shc. These results suggest that JAK kinase family members associated with the IL-6R may participate in the activation of MAP kinase in AF10 cells by way of an adaptor protein and Ras-dependent kinase cascade.
我们之前已经表明，在生长反应性B细胞系AF10中，IL-6受体可诱导丝裂原活化蛋白（MAP）激酶的激活。在此我们证明，在AF10细胞中，由IL-6诱导的MAP激酶级联反应中，Raf-1和MEK-1分别作为MAP激酶激酶激酶和MAP激酶激酶被激活。IL-6还诱导了AF10细胞中IL-6受体信号转导亚基的酪氨酸磷酸化，以及gp130相关酪氨酸蛋白激酶JAK1和衔接分子p52shc的酪氨酸磷酸化。尽管在分化反应性B细胞系SKW 6.4中，IL-6诱导的酪氨酸磷酸化和MAP激酶激活低于检测限，但佛波酯PMA确实激活了Raf-1、MEK-1和MAP激酶，而未诱导gp130、JAKs或p52shc的磷酸化。这些结果表明，与IL-6受体相关的JAK激酶家族成员可能通过衔接蛋白和Ras依赖性激酶级联反应参与AF10细胞中MAP激酶的激活。
