Abstract
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.
Highlights
Cytokines activate intracellular signaling pathways during growth and differentiation responses
STAT5A and STAT5B are two highly related proteins that share 96% homology. These proteins differ at their COOH terminus, a region highly variable among other STAT proteins that is thought to be involved in transcriptional activation
In this report we showed that STAT5A and STAT5B homodimers have distinct DNA binding specificities
Summary
Vol 273, No 51, Issue of December 18, pp. 33936 –33941, 1998 Printed in U.S.A. A Single Amino Acid in the DNA Binding Regions of STAT5A and STAT5B Confers Distinct DNA Binding Specificities*. Chimeric STAT5 molecules allowed us to identify a region between amino acid 420 and 545 responsible for the DNA binding specificity. 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. The DNA binding region is located in the center of the STAT proteins (from amino acids 350 to 500), and the transactivation domain is present at their. Isoforms of STAT proteins that lack the COOH-terminal transactivation domain still bind to DNA but do not induce transcriptional activation of responsive genes [14]. -Casein(Ϫ150) -Casein(Ϫ105) APRE (␣2-macroglobulin) SIEm67(c-fos) IRF-1 I Cis Bcl-x
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