PTEN/MMAC1/TEP1 in signal transduction and tumorigenesis
PTEN/MMAC1/TEP1 in signal transduction and tumorigenesis
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DOI：
10.1046/j.1432-1327.1999.00542.x
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发表时间：
1999-08-01
期刊：
影响因子：
--
通讯作者：
Yong, VW
中科院分区：
文献类型：
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作者：
Besson, A;Robbins, SM;Yong, VW
细胞内的磷酸化水平受到蛋白激酶和蛋白磷酸酶协同作用的严格调控[Hunter，T.(1995)Cell 80,225-236]。这两个参与者中的任何一个的活动失调都会导致细胞转化。许多蛋白酪氨酸激酶是原癌基因，一些蛋白磷酸酶被认为可能是肿瘤抑制基因。在这里，我们将对候选肿瘤抑制基因PTEN/MMAC1/TEP1(PTEN，10号染色体缺失的磷酸酶和张力蛋白同源物；MMAC 1，在多种晚期癌症中突变1；TEP1，转化生长因子β调控和上皮细胞富集型磷酸酶I)在信号转导和肿瘤发生中所起的作用进行综述。PTEN是一种双特异性蛋白磷酸酶(针对磷酸化丝氨酸/苏氨酸和磷酸化酪氨酸)，出人意料的是，它还具有磷酸肌醇3-磷酸酶活性。PTEN通过催化PtdIns 3-Kinase产生的PtdIns(3，4，5)P-3的降解，在1-磷脂酰肌醇3-激酶(PtdIns 3-Kinase)途径的调节中发挥重要作用，从而抑制PtdIns 3-Kinase途径介导的下游功能，如蛋白激酶B(PKB，又称Akt)的激活、细胞存活和细胞增殖。此外，PTEN通过直接去磷酸化和抑制粘着斑激酶(FAK)来负向调节粘着斑处产生的信号，从而调控细胞的迁移和侵袭。生长因子受体信号也受到PTEN的负调控，通过抑制适配蛋白Shc来实现。虽然PTEN的一些功能已经被阐明，但很明显，关于这个独特的蛋白质的作用，还有更多的东西需要发现。
The level of phosphorylation within cells is tightly regulated by the concerted action of protein kinases and protein phosphatases [Hunter, T. (1995) Cell 80, 225-236]. Disregulation in the activity of either of these players can lead to cellular transformation. Many protein tyrosine kinases are proto-oncogenes and it has been postulated that some protein phosphatases may act as tumor suppressors. Herein we will review the recent findings addressing the roles the candidate tumor suppressor PTEN/MMAC1/TEP1 (PTEN, phosphatase and tensin homologue deleted from chromosome 10; MMAC 1, mutated in multiple advanced cancers 1; TEP1, TGF beta regulated and epithelial cell enriched phosphatase I) plays in signal transduction and tumorigenesis. PTEN is a dual specificity protein phosphatase (towards phospho-Ser/Thr and phospho-Tyr) and, unexpectedly, also has a phosphoinositide 3-phosphatase activity. PTEN plays an important role in the modulation of the 1-phosphatidylinositol 3-kinase (PtdIns 3-kinase) pathway, by catalyzing the degradation of the PtdIns(3,4,5)P-3 generated by PtdIns 3-kinase; this inhibits the downstream functions mediated by the PtdIns 3-kinase pathway, such as activation of protein kinase B (PKB, also known as Akt), cell survival and cell proliferation. Furthermore, PTEN modulates cell migration and invasion by negatively regulating the signals generated at the focal adhesions, through the direct dephosphorylation and inhibition of focal adhesion kinase (FAK). Growth factor receptor signaling is also negatively regulated by PTEN, through the inhibition of the adaptor protein Shc. While some of the functions of PTEN have been elucidated, it is clear that there is much more to discover about the roles of this unique protein.