STAT3 ACTIVATION BY CYTOKINES UTILIZING GP130 AND RELATED TRANSDUCERS INVOLVES A SECONDARY MODIFICATION REQUIRING AN H7-SENSITIVE KINASE
STAT3 ACTIVATION BY CYTOKINES UTILIZING GP130 AND RELATED TRANSDUCERS INVOLVES A SECONDARY MODIFICATION REQUIRING AN H7-SENSITIVE KINASE
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DOI：
10.1073/pnas.92.15.6915
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发表时间：
1995-07-18
影响因子：
11.1
通讯作者：
YANCOPOULOS, GD
中科院分区：
文献类型：
--
作者：
BOULTON, TG;ZHONG, Z;YANCOPOULOS, GD
睫状神经营养因子、制瘤素M、白血病抑制因子和白细胞介素6是相关的细胞因子，其通过使信号转导受体组分gp 130同源二聚化或通过使gp 130与gp 130相关受体组分异源二聚化来启动信号传导。受体二聚化反过来激活Jak/Tyk家族的受体相关激酶，导致几种细胞内蛋白的快速酪氨酸磷酸化，包括信号转导子和转录激活子（STAT）家族的两个成员--STAT 1和STAT 3。在此，我们表明，在所有检测的应答细胞中，所有利用gp 130的细胞因子依次诱导两种不同形式的STAT 3，这两种形式明显不同，因为涉及H7敏感性激酶的时间依赖性二级丝氨酸/苏氨酸磷酸化，虽然两种STAT 3形式都结合DNA并易位到细胞核，但从一种形式到另一种形式的显著时间依赖性进展暗示了两种形式之间的其他重要功能差异，粒细胞集落刺激因子利用与gp 130高度相关的受体，也诱导这两种形式的STAT 3。与STAT 1相比，使用gp 130和相关信号转导子的所有细胞因子一致地和优先地诱导两种形式的STAT 3;无论在特定应答中使用哪种Jak/Tyk激酶，都可以看到这种特征性STAT激活模式，这与受体组分本身是激活哪种STAT的主要决定因素的概念一致。
Ciliary neurotrophic factor, oncostatin M, leukemia-inhibitory factor, and interleukin 6 are related cytokines that initiate signaling by homodimerizing the signal-transducing receptor component gp130 or by heterodimerizing gp130 with a gp130-related receptor component, Receptor dimerization in turn activates receptor-associated kinases of the Jak/Tyk family, resulting in the rapid tyrosine phosphorylation of several intracellular proteins, including those of two members of the signal transducers and activators of transcription (STAT) family-STAT1 and STAT3, Here we show that all cytokines that utilize gp130 sequentially induce two distinct forms of STAT3 in all responding cells examined, with the two forms apparently differing because of a time-dependent secondary serine/threonine phosphorylation involving an H7-sensitive kinase, While both STAT3 forms bind DNA and translocate to the nucleus, the striking time-dependent progression from one form to the other implies other important functional differences between the two forms, Granulocyte colony-stimulating factor, which utilizes a receptor highly related to gp130, also induces these two forms of STAT3, In contrast to a number of other cytokines and growth factors, all cytokines using gp130 and related signal transducers consistently and preferentially induce the two forms of STAT3 as compared with STAT1; this characteristic STAT activation pattern is seen regardless of which Jak/Tyk kinases are used in a particular response, consistent with the notion that the receptor components themselves are the primary determinants of which STATs are activated.