Sliva D, Wood T J, Schindler C, Lobie P E, Norstedt G
Center for Biotechnology, Karolinska Institute, NOVUM, Huddinge, Sweden.
J Biol Chem. 1994 Oct 21;269(42):26208-14.
Growth hormone activates gene transcription of the serine protease inhibitors (SPI) 2.1 and 2.2 by an unknown mechanism. In order to define the promoter regions responsible for this effect and to characterize the transcription factors involved, we have performed gel electrophoresis mobility shift assays on nuclear extracts from cell lines transfected with growth hormone receptor cDNA. We have identified a 9-base pair DNA element, the SPI-GLE 1, which forms a complex with nuclear proteins following activation by growth hormone and which, when placed upstream of a minimal thymidine kinase promoter, drives chloramphenicol acetyltransferase expression in a growth hormone-dependent fashion. This element is similar to those from several genes regulated by other cytokines including interferon. The growth hormone-induced complexes formed were dependent on tyrosine phosphorylation but did not contain the interferon-gamma-activated transcription factor Stat 91. Competition studies with oligonucleotides similar to the SPI-GLE 1 reveal the sequence of a consensus element that specifically binds growth hormone-regulated nuclear proteins.
生长激素通过未知机制激活丝氨酸蛋白酶抑制剂（SPI）2.1和2.2的基因转录。为了确定负责此效应的启动子区域并表征所涉及的转录因子，我们对转染了生长激素受体cDNA的细胞系的核提取物进行了凝胶电泳迁移率变动分析。我们鉴定出一个9个碱基对的DNA元件，即SPI-GLE 1，它在生长激素激活后与核蛋白形成复合物，并且当置于最小胸苷激酶启动子上游时，以生长激素依赖的方式驱动氯霉素乙酰转移酶表达。该元件类似于受其他细胞因子（包括干扰素）调节的几个基因的元件。形成的生长激素诱导复合物依赖于酪氨酸磷酸化，但不包含干扰素-γ激活的转录因子Stat 91。与类似于SPI-GLE 1的寡核苷酸的竞争研究揭示了特异性结合生长激素调节的核蛋白的共有元件序列。
