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J. Biol. Chem., Vol. 278, Issue 19, 17218-17227, May 9, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/19/17218    most recent M301578200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kabotyanski, E. B. Articles by Rosen, J. M. Search for Related Content PubMed PubMed Citation Articles by Kabotyanski, E. B. Articles by Rosen, J. M. Social Bookmarking                      What's this?

Signal Transduction Pathways Regulated by Prolactin and Src Result in Different Conformations of Activated Stat5b^*

Elena B. Kabotyanski and Jeffrey M. Rosen

From the Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030-3498

Stat5 is activated by a broad spectrum of cytokines, as well as non-receptor tyrosine kinases, such as Src. In this study, the DNA binding properties of the two closely related Stat5 proteins, Stat5a and Stat5b, induced either by prolactin (Prl) or by Src were analyzed by electrophoretic mobility shift assays using several different Stat5 binding sites. Src-induced Stat5b-DNA binding complexes consistently displayed a slightly faster mobility than those induced by Prl, as well as differences in their ability to be supershifted by anti-Stat5 antibodies. IP-Westerns performed using specific antibodies directed at the N and C termini of Stat5b suggested that depending on the activating stimulus, Stat5b exhibited different conformations, which influenced antibody accessibility at its C terminus. These conformational differences may in part be due to differential effects of Prl and Src on Stat5b tyrosine phosphorylation, since Src induced several additional sites of tyrosine phosphorylation of Stat5b at residues other than Tyr-699, including Tyr-724 and Tyr-679. The latter Tyr-679 is conserved in all mammalian Stat5bs, but is not present in Stat5a. A Stat 5bY679F mutant induced by Src kinase exhibited an altered pattern of nuclear localization as compared with wild-type Stat5b. Furthermore, this mutation inhibited v-Src-induced cyclin D1-luciferase reporter activity in transient transfection assays performed in Stat5a/b-deficient MEFs, suggesting that Tyr-679 phosphorylation may play a role in v-Src induced proliferation. Thus, depending on the signal transduction pathway responsible for activation, different conformations of activated Stat5 may result in selective biological responses.

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