MODULATION OF THE GLYCOGEN-SYNTHASE KINASE-3 FAMILY BY TYROSINE PHOSPHORYLATION
MODULATION OF THE GLYCOGEN-SYNTHASE KINASE-3 FAMILY BY TYROSINE PHOSPHORYLATION
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DOI：
10.1002/j.1460-2075.1993.tb05715.x
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发表时间：
1993-02-01
期刊：
影响因子：
11.4
通讯作者：
WOODGETT, JR
中科院分区：
文献类型：
--
作者：
HUGHES, K;NIKOLAKAKI, E;WOODGETT, JR
糖原合成酶激酶-3 （GSK-3）是一种蛋白丝氨酸激酶，与细胞对胰岛素的反应有关。该酶是黑腹果蝇的zete -white3（蓬松）同源基因的哺乳动物同源物，并与c-Jun/AP-1转录因子的调节有关。在哺乳动物中，这种蛋白丝氨酸激酶由两个相关基因编码，称为gsk -3 α和β。在这里，我们证明了这两种蛋白和果蝇蛋白在体内酪氨酸上被磷酸化。此外，gsk -3 β的活性和功能依赖于酪氨酸磷酸化。修饰后的酪氨酸残基在GSK-3家族的所有成员中都是保守的，并且与丝裂原活化蛋白（MAP）激酶的活性所需的氨基酸残基相当。然而，与MAP激酶不同，GSK-3在酪氨酸上高度磷酸化，因此在静息细胞中具有活性。
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-3alpha and beta. Here, we demonstrate that these two proteins and the fruit fly protein are phosphorylated on tyrosine in vivo. Moreover, GSK-3beta 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.