Modulation of the glycogen synthase kinase-3 family by tyrosine phosphorylation.
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.
Ludwig Institute for Cancer Research, London, UK.
K
K
Hughes
E
E
Nikolakaki
S E
SE
Plyte
N F
NF
Totty
J R
JR
Woodgett
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002417:Cattle; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004247:DNA; D038341:Glycogen Synthase Kinases; D006801:Humans; D008969:Molecular Sequence Data; D009036:Moths; D010766:Phosphorylation; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D017386:Sequence Homology, Amino Acid; D014443:Tyrosine / Q000378:metabolism*
D014443:Tyrosine; D004247:DNA; D011494:Protein Kinases; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases