Theill L E, Hattori K, Lazzaro D, Castrillo J L, Karin M
Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla 92093-0636.
EMBO J. 1992 Jun;11(6):2261-9. doi: 10.1002/j.1460-2075.1992.tb05285.x.
The POU domain protein GHF-1 has a critical role in generation, proliferation and phenotypic expression of three pituitary cell types. GHF-1 functions in part by binding to and transactivating the promoters of both the growth hormone (GH) and prolactin (PRL) genes and that of the GHF1 gene itself. We describe a naturally occurring isoform of GHF-1, GHF-2, in which an additional 26 amino acids are inserted into the activation domain of the protein as a result of alternative splicing. GHF-2 retains the DNA binding activity of GHF-1 and can activate the GH promoter but has lost the ability to activate the PRL and GHF1 promoters. These results suggest that GHF-2 may function in differential target gene activation during differentiation of the somatotrophic lineage. Both GHF-1 and GHF-2 transcripts are specifically expressed in the anterior pituitary. Analysis of the genomic GHF1 gene shows that most of the distinct functional domains of GHF-1 (and GHF-2) are encoded by separate exons. Gene segment duplication and exon shuffling may have contributed to the evolution of this cell type-specific transcriptional regulatory gene.
POU结构域蛋白GHF-1在三种垂体细胞类型的生成、增殖和表型表达中起关键作用。GHF-1部分通过结合并反式激活生长激素（GH）基因、催乳素（PRL）基因以及GHF1基因本身的启动子来发挥功能。我们描述了一种天然存在的GHF-1同工型，即GHF-2，由于选择性剪接，该蛋白的激活结构域中额外插入了26个氨基酸。GHF-2保留了GHF-1的DNA结合活性，能够激活GH启动子，但失去了激活PRL和GHF1启动子的能力。这些结果表明，GHF-2可能在生长激素细胞系分化过程中的差异靶基因激活中发挥作用。GHF-1和GHF-2转录本均在前叶垂体中特异性表达。对基因组GHF1基因的分析表明，GHF-1（和GHF-2）的大多数不同功能结构域由单独的外显子编码。基因片段重复和外显子重排可能促进了这种细胞类型特异性转录调节基因的进化。
