Expression, localization, and activity of glycogen synthase kinase 3β during mouse skin tumorigenesis
Expression, localization, and activity of glycogen synthase kinase 3β during mouse skin tumorigenesis
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DOI：
10.1002/mc.10087
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发表时间：
2002-12-01
影响因子：
4.6
通讯作者：
Paramio, JM
中科院分区：
文献类型：
--
作者：
Leis, H;Segrelles, C;Paramio, JM
糖原合成酶激酶3（GSK-3）是一种蛋白激酶，在控制几种发育、代谢和凋亡过程中起重要作用。由于其对几种致癌损伤的负作用，它被认为是一种假定的功能性肿瘤抑制剂。我们研究了GSK-3 β在化学诱导的两阶段小鼠皮肤癌发生过程中的表达、活性和定位，以及皮下注射Akt转化的角质形成细胞后产生的肿瘤中的表达、活性和定位。我们发现，GSK-3活性下调，在后期阶段的促进酪氨酸216去磷酸化和丝氨酸9磷酸化。用Akt转化的角质形成细胞获得的数据清楚地表明Akt参与GSK-3 β的丝氨酸9磷酸化。最后，除了功能失活外，在所有情况下均检测到GSK-3 β的显著基础活性，表明这种酶为恶性角质形成细胞提供了必要的功能。(C)2002 Wiley-Liss，Inc.
Glycogen synthase kinase 3 (GSK-3) is a protein kinase that plays essential roles in the control of several developmental, metabolic, and apoptotic processes. Owing to its negative actions on several oncogenic insults, it has been considered a putative functional tumor suppressor. We studied the expression, activity, and localization of GSK-3beta during the process of chemically induced two-stage mouse skin carcinogenesis and also in the tumors generated upon subcutaneous injection of Akt-transformed keratinocytes. We found that GSK-3 activity was downregulated at the later stages of promotion by tyrosine 216 dephosphorylation and serine 9 phosphorylation. The data obtained with Akt-transformed keratinocytes clearly suggested the involvement of Akt in serine 9 phosphorylation of GSK-3beta. Finally, besides functional inactivation, significant basal activity of GSK-3beta was detected in all cases, indicating that this enzyme provides essential functions to malignant keratinocytes. (C) 2002 Wiley-Liss, Inc.