Constitutive nuclear import of latent and activated STAT5a by its coiled coil domain Janaki Iyer and Nancy C. Reich 1 Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, USA 1 Correspondence: Dept. of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794, USA. E-mail: nreich@notes.cc.sunysb.edu Signal transducer and activator of transcription 5a (STAT5a) is a critical transcription factor for a number of physiological processes including hematopoiesis and mammary gland development. Cytokines such as growth hormone, prolactin, erythropoietin, and interleukin-2 stimulate the activation of STAT5a by tyrosine phosphorylation. Tyrosine phosphorylation confers a conformational change and the ability to bind specific target DNA. To execute its function as a signaling molecule and transcription factor, accurate cellular localization of STAT5a is essential. This study explores the nuclear trafficking of STAT5a both before phosphorylation and after tyrosine phosphorylation. With the use of live cell imaging we demonstrate the continuous shuttling of STAT5a in and out of the nucleus. Evaluation of a series of mutations and deletions identifies a region within the coiled coil domain of STAT5a that is critical for nuclear import of both unphosphorylated and tyrosine-phosphorylated forms. The mechanism that regulates transport of STAT5a through nuclear pore complexes into the nucleus is therefore independent of tyrosine phosphorylation. However, after tyrosine phosphorylation, STAT5a accumulates in the nucleus because of its retention by DNA binding. These findings should provide a foundation for further studies that involve targeting the activity of STAT5a.—Iyer, J., Reich, N. C. Constitutive nuclear import of latent and activated STAT5a by its coiled coil domain. Key Words: transcription factor • nuclear trafficking • tyrosine phosphorylation • live cell imaging
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Constitutive nuclear import of latent and activated STAT5a by its coiled coil domain
Iyer, Janaki; Reich, Nancy C.
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, Volume 22 (2): 391
Fed of American Socs for Experimental Biology – Feb 1, 2008
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