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J. Biol. Chem., Vol. 278, Issue 36, 34133-34140, September 5, 2003

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STATs Dimerize in the Absence of Phosphorylation^*

Jutta Braunstein  , Siska Brutsaert  ¶ ||, Rich Olson ** and Christian Schindler   

From the Departments of Microbiology, ^**Biochemistry & Medicine, and the ^¶Integrated Graduate Program, Columbia University, New York, New York 10032

Upon activation by tyrosine kinases, members of the STAT family of transcription factors form stable dimers that are able to rapidly translocate to the nucleus and bind DNA. Although crystal structures of activated, near full-length, Stat1 and Stat3 illustrate how STATs bind to DNA, they provide little insight into the dynamic regulation of STAT activity. To explore the unique structural changes Stat1 and Stat3 undergo when they become activated, full-length inactive recombinant proteins were prepared. To our surprise, even though these proteins are unable to bind DNA, our studies demonstrate that they exist as stable homodimers. Similarly, the Stat1 and Stat3 found in the cytoplasm of unstimulated cells also exhibit a dimeric structure. These observations indicate that Stat1 and Stat3 exist as stable homodimers prior to activation.

Received for publication, April 30, 2003 , and in revised form, June 17, 2003.

^* This work was supported in part by National Institutes of Health (NIH) Grants HL55413 and S10RR12848 and Human Frontier Science Program Grant RG0166/2000. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Supported by Deutsche Forschungsgemeinschaft Grant Br 1875/1-1 and by a Jane Morse Fellowship.

^|| Supported by NIH Training Grant T32 DK07328.

To whom correspondence should be addressed: Columbia University, HHSC 1208, 701 West 168th St., New York, NY 10032. Tel.: 212-305-5380; Fax: 212-543-0063; E-mail: cws4{at}columbia.edu.

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