文章：

蛋白质-酪氨酸磷酸酶与癌症

Protein-tyrosine phosphatases and cancer

原文发布日期：2006-04-01

DOI: 10.1038/nrc1837

类型: Review Article

开放获取: 否

要点：

1. Protein-tyrosine phosphatases (PTPs) constitute a structurally diverse family of tightly regulated enzymes that are characterized by a conserved catalytic domain with an oxidation-sensitive active-site cysteine residue.
2. Different PTPs function as negative or positive mediators of signalling triggered by receptor-tyrosine kinases, integrins and cell-adhesion molecules.
3. The tumour-suppressive function of PTPs is indicated by frequent inactivating mutations of PTPs in colon cancer, and the identification of Ptprj as the gene that confers colon cancer susceptibility in STS/A mice. Also, inactivation of the genes that encode SHP1 and glomerular epithelial protein 1 (GLEPP1) by methylation has been described in haematological malignancies and solid tumours, respectively.
4. The oncogenic activity of a PTP is best characterized for the mutational activation of SHP2, which occurs in hereditary and sporadic leukaemias and, less frequently, in solid tumours.
5. Despite technical challenges, recent advances in the design of PTP inhibitors are encouraging with respect to the possibilities of developing novel cancer drugs that function by inhibiting oncogenic PTPs.
6. Other aspects of PTP biology that might be relevant to cancer research in the future are the regulation of PTPs by oxidation and the putative role of PTPs in angiogenesis.

要点翻译：

1. 蛋白酪氨酸磷酸酶（PTPs）是一个结构多样、调控严密的酶家族，其标志性特征为具有含氧化敏感性活性中心半胱氨酸残基的保守催化结构域。
2. 不同PTPs在受体酪氨酸激酶、整合素及细胞黏附分子触发的信号传导中发挥负向或正向调控作用。
3. PTPs的抑癌功能通过以下发现得以证实：结肠癌中频繁出现PTPs失活突变；Ptprj基因被鉴定为STS/A小鼠结肠癌易感基因。此外，研究报道SHP1和肾小球上皮蛋白1（GLEPP1）编码基因分别通过甲基化失活，见于血液系统恶性肿瘤和实体瘤。
4. PTPs的致癌活性最典型的例证是SHP2的突变激活，该突变见于遗传性和散发性白血病，在实体瘤中发生频率较低。
5. 尽管存在技术挑战，PTP抑制剂设计的最新进展为开发通过抑制致癌性PTPs发挥作用的新型抗癌药物带来了希望。
6. 未来可能与癌症研究相关的PTP生物学其他方面包括：氧化对PTPs的调控作用，以及PTPs在血管生成中的推定功能。

英文摘要：

Tyrosine phosphorylation is an important signalling mechanism in eukaryotic cells. In cancer, oncogenic activation of tyrosine kinases is a common feature, and novel anticancer drugs have been introduced that target these enzymes. Tyrosine phosphorylation is also controlled by protein-tyrosine phosphatases (PTPs). Recent evidence has shown that PTPs can function as tumour suppressors. In addition, some PTPs, including SHP2, positively regulate the signalling of growth-factor receptors, and can be oncogenic. An improved understanding of how these enzymes function and how they are regulated might aid the development of new anticancer agents.

摘要翻译： 

酪氨酸磷酸化是真核细胞中一种重要的信号传导机制。在癌症中，酪氨酸激酶的致癌性激活是一种常见特征，并已引入了针对这些酶的新型抗癌药物。酪氨酸磷酸化也受到蛋白酪氨酸磷酸酶（PTPs）的调控。最新证据表明，PTPs可以发挥肿瘤抑制作用。此外，包括SHP2在内的一些PTPs能够正向调控生长因子受体的信号传导，并且可能具有致癌性。更深入地理解这些酶的功能及其调控机制，可能有助于开发新的抗癌药物。

原文链接：

Protein-tyrosine phosphatases and cancer