Protein Tyrosine Phosphatases as Potential Regulators of STAT3 Signaling.
Protein Tyrosine Phosphatases as Potential Regulators of STAT3 Signaling.
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DOI：
10.3390/ijms19092708
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发表时间：
2018-09-11
影响因子：
5.6
通讯作者：
Kim DJ
中科院分区：
文献类型：
--
作者：
Kim M;Morales LD;Jang IS;Cho YY;Kim DJ
信号转导和转录激活子3(STAT3)蛋白是一种主要的转录因子，参与细胞的生长、增殖、分化、迁移、细胞死亡或细胞凋亡等多种细胞过程。它在各种细胞外刺激下被激活，包括细胞因子和生长因子。STAT3的异常激活导致了几种人类疾病，特别是癌症。因此，STAT3介导的信号转导继续被广泛研究，以确定开发新的和更有效的临床治疗的潜在靶点。STAT3的激活可以通过不同的翻译后机制来调节，无论是积极的还是消极的，包括丝氨酸或酪氨酸的磷酸化/去磷酸化、乙酰化或去甲基化。负调控STAT3活性的主要机制之一是酪氨酸残基的去磷酸化，而酪氨酸残基是蛋白酪氨酸磷酸酶(PTPs)激活STAT3所必需的。已证实有7种PTPs可使STAT3去磷酸化，从而调节STAT3信号转导：PTP受体D型(PTPRD)、PTP受体T型(PTPRT)、PTP受体K型(PTPRK)、Src同源区2(SH-2)含结构域的磷酸酶1(SHP1)、含SH-2结构域的磷酸酶2(SHP2)、MEG2/PTP非受体类型9(PTPN9)和T细胞PTP(TC-PTP)/PTP非受体类型2(PTPN2)。这些监管机构在开发更有效的治疗人类疾病(包括癌症)方面具有巨大的潜力。
The signal transducer and activator of transcription 3 (STAT3) protein is a major transcription factor involved in many cellular processes, such as cell growth and proliferation, differentiation, migration, and cell death or cell apoptosis. It is activated in response to a variety of extracellular stimuli including cytokines and growth factors. The aberrant activation of STAT3 contributes to several human diseases, particularly cancer. Consequently, STAT3-mediated signaling continues to be extensively studied in order to identify potential targets for the development of new and more effective clinical therapeutics. STAT3 activation can be regulated, either positively or negatively, by different posttranslational mechanisms including serine or tyrosine phosphorylation/dephosphorylation, acetylation, or demethylation. One of the major mechanisms that negatively regulates STAT3 activation is dephosphorylation of the tyrosine residue essential for its activation by protein tyrosine phosphatases (PTPs). There are seven PTPs that have been shown to dephosphorylate STAT3 and, thereby, regulate STAT3 signaling: PTP receptor-type D (PTPRD), PTP receptor-type T (PTPRT), PTP receptor-type K (PTPRK), Src homology region 2 (SH-2) domain-containing phosphatase 1(SHP1), SH-2 domain-containing phosphatase 2 (SHP2), MEG2/PTP non-receptor type 9 (PTPN9), and T-cell PTP (TC-PTP)/PTP non-receptor type 2 (PTPN2). These regulators have great potential as targets for the development of more effective therapies against human disease, including cancer.
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影响因子：
3.5
作者：
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通讯作者：
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