A single amino acid in the DNA binding regions of STAT5A and STAT5B confers distinct DNA binding specificities

STAT5A and STAT5B are two highly related transcription factors encoded by t wo distinct genes. STAT5A and STAT5B are activated by a broad range of cyto kines and growth factors, Although they can be differentially activated, th e functional difference between these two molecules relative to their struc ture is not known. Here we demonstrated that STAT5A and STAT5B homodimers h ave distinct DNA binding preferences; Chimeric STATE molecules allowed us t o 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 an d STAT5B from different species showed a difference of 5 amino acids in the region 420-545 between STAT5A and STAT5B. Substitution of these amino acid s demonstrated that a glycine residue at position 433 in STAT5B and a gluta mic residue at a similar position in STAT5A determined the DNA binding spec ificity. These data indicate that STAT5A and STAT5B homodimers may have dis tinct function and probably regulate the expression of common as well as di stinct genes.