SHP-1 in Cell-Cycle Regulation
SHP-1 in Cell-Cycle Regulation
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DOI：
10.2174/187152011794941154
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发表时间：
2011-01-01
影响因子：
2.8
通讯作者：
Colas, Begona
中科院分区：
文献类型：
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作者：
Lopez-Ruiz, Pilar;Rodriguez-Ubreva, Javier;Colas, Begona
蛋白质中酪氨酸残基的可逆磷酸化是由蛋白酪氨酸激酶（PTKs）和蛋白酪氨酸磷酸酶（PTPs）的平衡作用所控制的，是参与控制细胞增殖的信号通路的关键要素。这些关键调节因子中的任何一个解除管制都会导致细胞信号传导异常，这在很大程度上与包括癌症在内的人类病理有关。本文综述了酪氨酸磷酸酶SHP-1在细胞周期调控中的作用及其在肿瘤发生和发展中的可能作用。SHP-1是一种具有两个SH2结构域的PTP，在造血细胞中表达，并在许多其他细胞类型中表达，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组成部分，如CDK2、p27和cyclin D1。由于几种靶向SHP-1的抑制剂已经证明了它们在癌症治疗中的价值，这种磷酸酶被认为是这种病理的治疗靶点。
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.