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 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.
Boucheron
C
C
Institut Cochin de Génétique Moléculaire (ICGM), INSERM U363, Hôpital Cochin, 27 rue du Fbg St Jacques, 75014 Paris, France.
Dumon
S
S
Santos
S C
SC
Moriggl
R
R
Hennighausen
L
L
Gisselbrecht
S
S
Gouilleux
F
F
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D019556:COS Cells; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D015342:DNA Probes; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D005998:Glycine; D006801:Humans; D051379:Mice; D008894:Milk Proteins; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D050799:STAT5 Transcription Factor; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection; D025521:Tumor Suppressor Proteins
D015342:DNA Probes; D004268:DNA-Binding Proteins; D008894:Milk Proteins; D011993:Recombinant Fusion Proteins; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; C494095:STAT5B protein, human; C494093:Stat5a protein, mouse; C494096:Stat5b protein, mouse; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D004247:DNA; D005998:Glycine