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. 1993 Feb;12(2):803–808. doi: 10.1002/j.1460-2075.1993.tb05715.x

Modulation of the glycogen synthase kinase-3 family by tyrosine phosphorylation.

K Hughes 1, E Nikolakaki 1, S E Plyte 1, N F Totty 1, J R Woodgett 1
PMCID: PMC413270  PMID: 8382613

Abstract

Glycogen synthase kinase-3 (GSK-3) is a protein serine kinase implicated in the cellular response to insulin. The enzyme is the mammalian homologue of the zeste-white3 (shaggy) homeotic gene of Drosophila melanogaster and has been implicated in the regulation of the c-Jun/AP-1 transcription factor. In mammals this protein serine kinase is encoded by two related genes termed GSK-3 alpha and beta. Here, we demonstrate that these two proteins and the fruit fly protein are phosphorylated on tyrosine in vivo. Moreover, GSK-3 beta activity and function are shown to be dependent on tyrosine phosphorylation. The modified tyrosine residue is conserved in all members of the GSK-3 family and is equivalent to that required for activity by mitogen-activated protein (MAP) kinases. However, unlike MAP kinases, GSK-3 is highly phosphorylated on tyrosine and thus active in resting cells.

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