Department of Biochemistry and Molecular Biology, University of Alcalá, Alcalá de Henares, Madrid, Spain.
Anticancer Agents Med Chem. 2011 Jan;11(1):89-98. doi: 10.2174/187152011794941154.
The reversible phosphorylation of tyrosine residues in proteins, which is governed by the balanced action of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs), is a key element of the signaling pathways that are involved in the control of cell proliferation. Deregulation of either of these key regulators leads to abnormal cell signaling, which is largely associated with human pathologies including cancer. This review focuses on recent studies on the role of the protein tyrosine phosphatase SHP-1 on cell-cycle regulation and its possible roles in tumour onset and progression. SHP-1 is a PTP with two SH2 domains that is expressed in haematopoietic cells and, moderately, in many other cell types, especially malignant epithelial cells. SHP-1 regulates cell proliferation, whether it is by controlling mitogenic pathways activated by receptors with tyrosine kinase activity, or by regulating components of the cell-cycle machinery such as CDK2, p27 and cyclin D1. Since several inhibitors targeting SHP-1 have demonstrated their value in cancer treatment, this phosphatase has been proposed as a therapeutic target for this pathology.
蛋白质中酪氨酸残基的可逆磷酸化由蛋白酪氨酸激酶（PTKs）和蛋白酪氨酸磷酸酶（PTPs）的平衡作用所调控，是参与细胞增殖调控的信号通路的关键要素。这两个关键调控因子的失调会导致异常的细胞信号转导，这在很大程度上与包括癌症在内的人类病理有关。本篇综述重点介绍了蛋白酪氨酸磷酸酶 SHP-1 在细胞周期调控中的作用及其在肿瘤发生和进展中的可能作用的最新研究。SHP-1 是一种具有两个 SH2 结构域的 PTP，在造血细胞中表达，在许多其他细胞类型中也有中等程度的表达，尤其是恶性上皮细胞。SHP-1 调节细胞增殖，无论是通过控制具有酪氨酸激酶活性的受体激活的有丝分裂途径，还是通过调节细胞周期机制的成分，如 CDK2、p27 和 cyclin D1。由于几种针对 SHP-1 的抑制剂已证明在癌症治疗中的价值，因此该磷酸酶已被提议作为该病理的治疗靶点。
