| First Author | Gowri PM | Year | 2001 |
| Journal | J Biol Chem | Volume | 276 |
| Issue | 13 | Pages | 10485-91 |
| PubMed ID | 11133982 | Mgi Jnum | J:113883 |
| Mgi Id | MGI:3687795 | Doi | 10.1074/jbc.M007156200 |
| Citation | Gowri PM, et al. (2001) Conversion of threonine 757 to valine enhances Stat5a transactivation potential. J Biol Chem 276(13):10485-91 |
| abstractText | The growth hormone family of cytokines transduces intracellular signals through the Jak2-Stat5 pathway to activate the transcription of target genes. Amino acids within the C termini of Stats constitute the transactivation domain but also regulate the time course of tyrosine phosphorylation and extent of DNA binding. We mutated Thr(757) in the C-terminal of Stat5a (Thr-Stat5) to Val (Val-Stat5) and Asp (Asp-Stat5) and examined the effect on nuclear translocation, DNA binding, and prolactin-induced transcriptional activation of a Stat5-responsive luciferase reporter gene. Val-Stat5 produced a 5-fold higher increase in transcriptional activity relative to Thr-Stat5; Asp-Stat5 produced a similar response to Thr-Stat5. The increased transactivation was ligand induced and was not due to differences in basal expression of Val-Stat5 or to a constitutively activated Stat5 protein. Similar rates of loss of DNA binding ability and phosphorylation of Val- and Thr-Stat5 were observed following a single pulse of prolactin, indicating that the dephosphorylation pathways were unaltered. The serine-threonine kinase inhibitor H7 inhibited the transactivation potential of Thr-, Val-, and Asp-Stat5 to a similar extent, eliminating phosphorylation of Thr(757) as a regulatory mechanism. The results suggest that Thr(757) modulates the transactivation potential of Stat5 by a mechanism(s) that is dependent on the formation of Stat5 dimers and/or their nuclear translocation. |
