STAT5b mediates the GH-induced expression of SOCS-2 and SOCS-3 mRNA in the liver
STAT5b mediates the GH-induced expression of SOCS-2 and SOCS-3 mRNA in the liver
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DOI：
10.1016/s0303-7207(99)00175-6
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发表时间：
1999-12-20
影响因子：
4.1
通讯作者：
Adams, TE
中科院分区：
文献类型：
--
作者：
Davey, HW;McLachlan, MJ;Adams, TE
细胞因子信号转导抑制因子（SOCS）蛋白是调节细胞因子信号转导的经典负反馈环的一部分。SOCS蛋白的表达响应于细胞因子而被诱导，并通过抑制JAK/STAT途径下调细胞因子信号。先前显示生长激素（GH）在小鼠肝脏中诱导SOCS-3的强瞬时表达，并在较小程度上诱导CIS、SOCS-1和SOCS-2的瞬时表达（亚当斯，T.E.，汉森，J.A.，斯塔尔河，Nicola，N.A.，希尔顿，D. J.，Billestrup，N.，1998.生长激素优先诱导SOCS-3的快速，瞬时表达，SOCS-3是一种新型的细胞因子受体信号传导抑制剂。J.Biol.Chem.273，1285-1287）。在这项工作中，我们比较了GH诱导的野生型和STAT 5 b缺陷小鼠的SOCS基因表达，并表明：STAT 5 b是SOCS-2和SOCS-3在肝脏中的诱导所必需的。相比之下，STAT 5 b的缺乏对GH诱导的乳腺中CIS和SOCS-2 mRNA的表达没有影响。令人惊讶的是，在GH给药后，野生型和STAT 5 b突变小鼠的乳腺中没有SOCS-3表达的活化。这些结果突出了STAT 5a/B对SOCS基因表达调控的组织特异性和因子特异性差异。(C)1999爱思唯尔科学爱尔兰有限公司保留所有权利。
Suppressor of cytokine signalling (SOCS) proteins act as part of a classical negative feedback loop regulating cytokine signal transduction. Expression of SOCS proteins is induced in response to cytokines and down-regulates the cytokine signal by inhibiting the JAK/STAT pathway. Growth hormone (GH) was previously shown to induce strong transient expression of SOCS-3 and to a lesser extent CIS, SOCS-1 and SOCS-2 in mouse liver (Adams, T.E., Hansen, J.A., Starr, R., Nicola, N.A., Hilton, D.J., Billestrup, N., 1998. Growth hormone preferentially induces the rapid, transient expression of SOCS-3, a novel inhibitor of,cytokine receptor signalling. J. Biol. Chem. 273, 1285-1287.). In this work we have compared GH-induced SOCS gene expression in wild-type and STAT5b-deficient mice, and show that: STAT5b is required for the induction of SOCS-2 and SOCS-3 in liver. In contrast, the absence of STAT5b has no effect on the GH-induced expression of CIS and SOCS-2 mRNA in the mammary gland. Suprisingly, there is no activation of SOCS-3 expression in mammary glands of wild-type and STAT5b mutant mice following GH administration. These results highlight both tissue- and factor-specific differences in the regulation of SOCS gene expression by STAT5a/b. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.