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

Ginger, R. S., Dalton, Emma Charlotte ORCID: https://orcid.org/0000-0002-3517-0742, Ryves, W. J., Fukuzawa, M., Williams, J. G. and Harwood, A. J. 2000. Glycogen synthase kinase-3 enhances nuclear export of a Dictyostelium STAT protein. The EMBO Journal 19 (20) , pp. 5483-5491. 10.1093/emboj/19.20.5483

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	R Medicine > R Medicine (General)
Publisher:	Nature Publishing Group
ISSN:	1460-2075
Last Modified:	28 Oct 2022 08:37
URI:	https://orca.cardiff.ac.uk/id/eprint/71452

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