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Molecular and Cellular Biology, October 2000, p. 7273-7281, Vol. 20, No. 19
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Regulation of STAT1 Nuclear Export by Jak1

Kerri Mowen and Michael David*

Department of Biology, University of California at San Diego, La Jolla, California 92093

Received 23 May 2000/Returned for modification 20 June 2000/Accepted 27 June 2000

Signal transducer and activator of transcription 1 (STAT1) mediates gene expression in response to cytokines and growth factors. Activation of STAT1 is achieved through its tyrosine phosphorylation, a process that involves Jak tyrosine kinases. Here we show that STAT1, although phosphorylated on Y701, is unable to localize in the nucleus in the absence of Jak1 or Jak1 kinase activity. In contrast, the nuclear accumulation of STAT1 in Tyk2-deficient cells remains intact. Nuclear presence of tyrosine-phosphorylated STAT1 could be restored in Jak1-deficient cells by leptomycin B, an inhibitor of nuclear export. Amino acids 197 to 205 of STAT1 were found to encode a leucine-rich nuclear export signal (NES). An Lright-arrowA mutation within the NES restored nuclear retention of STAT1 in Jak1-deficient cells. Impaired binding of the transcriptional coactivator CBP to tyrosine-phosphorylated STAT1 derived from Jak1-deficient cells offers a model for the intermolecular regulation of the nuclear export sequence.

* Corresponding author. Mailing address: University of California, San Diego, Department of Biology, Bonner Hall 3138, 9500 Gilman Drive, La Jolla, CA 92093-0322. Phone: (858) 822-1108. Fax: (858) 822-1106. E-mail:midavid{at}ucsd.edu.

Molecular and Cellular Biology, October 2000, p. 7273-7281, Vol. 20, No. 19
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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