Boucheron C, Dumon S, Santos S C, Moriggl R, Hennighausen L, Gisselbrecht S, Gouilleux F
Institut Cochin de Génétique Moléculaire (ICGM), INSERM U363, Hôpital Cochin, 27 rue du Fbg St Jacques, 75014 Paris, France.
J Biol Chem. 1998 Dec 18;273(51):33936-41. doi: 10.1074/jbc.273.51.33936.
STAT5A and STAT5B are two highly related transcription factors encoded by two distinct genes. STAT5A and STAT5B are activated by a broad range of cytokines and growth factors. Although they can be differentially activated, the functional difference between these two molecules relative to their structure is not known. Here we demonstrated that STAT5A and STAT5B homodimers have distinct DNA binding preferences. Chimeric STAT5 molecules allowed us to identify a region between amino acid 420 and 545 responsible for the DNA binding specificity. This region is located in the previously characterized DNA binding region of STAT proteins. Sequence comparison between STAT5A and STAT5B from different species showed a difference of 5 amino acids in the region 420-545 between STAT5A and STAT5B. Substitution of these amino acids demonstrated that a glycine residue at position 433 in STAT5B and a glutamic residue at a similar position in STAT5A determined the DNA binding specificity. These data indicate that STAT5A and STAT5B homodimers may have distinct function and probably regulate the expression of common as well as distinct genes.
STAT5A和STAT5B是由两个不同基因编码的两个高度相关的转录因子。STAT5A和STAT5B可被多种细胞因子和生长因子激活。尽管它们可以被不同程度地激活，但这两种分子在功能上相对于其结构的差异尚不清楚。在此，我们证明了STAT5A和STAT5B同二聚体具有不同的DNA结合偏好。嵌合STAT5分子使我们能够确定氨基酸420至545之间负责DNA结合特异性的区域。该区域位于STAT蛋白先前已表征的DNA结合区域内。来自不同物种的STAT5A和STAT5B之间的序列比较显示，STAT5A和STAT5B在420-545区域有5个氨基酸的差异。这些氨基酸的替换表明，STAT5B中第433位的甘氨酸残基和STAT5A中类似位置的谷氨酸残基决定了DNA结合特异性。这些数据表明，STAT5A和STAT5B同二聚体可能具有不同的功能，并且可能调节共同基因以及不同基因的表达。
