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  • The EMBO Journal (2000) 19, 5483 - 5491
  • doi:10.1093/emboj/19.20.5483

Glycogen synthase kinase-3 enhances nuclear export of a Dictyostelium STAT protein

Rebecca S. Ginger1,2,4, Emma C. Dalton3,4, W.Jonathan Ryves3, Masashi Fukuzawa1, Jeffrey G. Williams1 and Adrian J. Harwood3

  1. Department of Anatomy and Physiology, MSI/WTB Complex, University of Dundee, Dow Street, Dundee DD1 5EH, UK
  2. Present address: Unilever Research, Colworth House, Sharnbrook, Beds MK44 1LQ, UK
  3. MRC, Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK
  4. R.S.Ginger and E.C.Dalton contributed equally to this work

Correspondence to:

Adrian J. Harwood, E-mail: a.harwood@ucl.ac.uk

Received 16 May 2000; Accepted 21 August 2000; Revised 18 August 2000

Extracellular cAMP stimulates the rapid tyrosine phosphorylation and nuclear translocation of the Dictyostelium STAT protein Dd-STATa. Here we show that it also induces serine phosphorylation by GskA, a homologue of glycogen synthase kinase-3 (GSK-3). Tyrosine phosphorylation occurs within 10 s of stimulation, whereas serine phosphorylation takes 5 min, matching the kinetics observed for the cAMP regulation of GskA. Phosphorylation by GskA enhances nuclear export of Dd-STATa. The phosphorylated region, however, is not itself a nuclear export signal and we identify a region elsewhere in the protein that mediates nuclear export. These results suggest a biphasic regulation of Dd-STATa, in which extracellular cAMP initially directs nuclear import and then, via GskA, promotes its subsequent export. It also raises the possibility of an analogous regulation of STAT nuclear export in higher eukaryotes.

  • Keywords:

    • Dictyostelium discoideum,
    • GSK-3,
    • nuclear export,
    • serine phosphorylation,
    • STAT transcription factors