Zon L I, Gurish M F, Stevens R L, Mather C, Reynolds D S, Austen K F, Orkin S H
Department of Pediatrics, Harvard Medical School, Children's Hospital, Boston, Massachusetts 02115.
J Biol Chem. 1991 Dec 5;266(34):22948-53.
The transcription factors GATA-1, GATA-2, and GATA-3 were found to be expressed in several mouse and rat mast cell lines that contain mast cell carboxypeptidase A (MC-CPA) and other proteases in their cytoplasmic granules. GATA-1 mRNA was not detected in P815 cells, an immature mouse mastocytoma-derived cell line that lacks electron-dense granules and has low levels of secretory granule proteases. Because the 5'-flanking regions of the mouse and human MC-CPA genes contained a conserved GATA-binding motif 51 base pairs upstream of their translation initiation sites, the ability of GATA-binding proteins to regulate the promoter activity of the MC-CPA gene was examined in rat basophilic leukemia cells, mouse P815 cells, and transfected mouse P815 cells that expressed GATA-1. In all three mast cell lines, the promoter activity of the MC-CPA gene depended on the GATA binding site. GATA-1, GATA-2, and GATA-3 are thus the first DNA-binding proteins identified in mast cells which regulate the promoter activity of a gene that encodes a secretory granule protease.
转录因子GATA-1、GATA-2和GATA-3在几种小鼠和大鼠肥大细胞系中表达，这些细胞系的细胞质颗粒中含有肥大细胞羧肽酶A（MC-CPA）和其他蛋白酶。在P815细胞中未检测到GATA-1 mRNA，P815细胞是一种源自未成熟小鼠肥大细胞瘤的细胞系，缺乏电子致密颗粒且分泌颗粒蛋白酶水平较低。由于小鼠和人MC-CPA基因的5'侧翼区域在其翻译起始位点上游51个碱基对处含有一个保守的GATA结合基序，因此在大鼠嗜碱性白血病细胞、小鼠P815细胞和表达GATA-1的转染小鼠P815细胞中检测了GATA结合蛋白调节MC-CPA基因启动子活性的能力。在所有三种肥大细胞系中，MC-CPA基因的启动子活性均依赖于GATA结合位点。因此，GATA-1、GATA-2和GATA-3是在肥大细胞中鉴定出的首批调节编码分泌颗粒蛋白酶基因启动子活性的DNA结合蛋白。
