The coordinated action of protein tyrosine phosphatases and kinases in cell signaling.
The coordinated action of protein tyrosine phosphatases and kinases in cell signaling.
复制标题
DOI：
10.1016/0968-0004(94)90134-1
复制
发表时间：
1994-11
影响因子：
13.8
通讯作者：
Hong Sun;N. Tonks
中科院分区：
文献类型：
--
作者：
Hong Sun;N. Tonks
细胞生长和分化所需的酪氨酸磷酸化水平通过蛋白酪氨酸激酶（PTK）和蛋白酪氨酸磷酸酶（PTPs）的协调作用来实现。根据细胞环境，这两种类型的酶在信号传递过程中可能相互拮抗或合作。这些酶之间的不平衡可能会损害正常的细胞生长，导致细胞转化。PTKs和PTPs都已经进化到结构多样性的水平，使它们能够调节许多细胞过程，本文将重点介绍几个具体的例子，突出PTPs和PTKs之间的相互作用，在细胞信号转导。条件在确定编码PTP的基因的染色体定位方面已经取得了相当大的进展，目的是将图谱位置与人类疾病状态中的异常位点相关联。新的和诱人的结果经常被报道。最值得注意的是染色体3 p21上的PTP~/基因，这是一个在肾和小细胞肺癌中经常改变的片段。现在看来，突变可能发生在PTP的细胞外片段中，因此可能产生不再对其外部信号作出反应的受体样PTP。几项研究报道了PTP对组织培养系统中细胞转化的抑制作用。PTPIB的表达已显示阻断由Neu 3介导的转化并部分逆转由Src 4介导的转化，这两者都是致癌PTK。研究表明，密切相关的磷酸酶TCPTP的表达可以部分逆转由Fins（一种失调的集落刺激因子受体）转化的细胞的形态表型。至少在TCPTP的情况下，已发现反式EkB的逆转与酪氨酰磷酸化蛋白质的子集的消失相一致，表明PTP在体内具有一定程度的底物特异性。PTP的靶点可能是PTK本身或PTK的底物（图1）。虽然需要更全面的研究来确定转化表型的关键底物，但迄今为止的结果传达了这样一种观点，即PTP可能是正常细胞和致癌PTK作用的强大拮抗剂。最近，一个细胞质PTP的生长抑制功能的特点，说明了权力的遗传方法来阐明PTP功能。HCP（也称为PTP 1C、SH-PTP 1或SHP;综述见参考文献6、7）是一种造血细胞PTP，其特征在于其氨基末端片段中有两个Src同源2（SH 2）结构域。SH 2结构域已显示结合限定的一级序列中的磷酸酪氨酸残基。编码HCP的基因中的突变导致其
The levels of tyrosine phosphorylation required for cell growth and differentiation are achieved through the coordinated action of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Depending upon the cellular context, these two types of enzymes may either antagonize or cooperate with each other during the signal transmission process. An imbalance between these enzymes may impair normal cell growth, leading to cellular transformation. Both PTKs and PTPs have evolved to a level of structural diversity that allows them to regulate many cellular processes, This review will focus on several specific examples that highlight the interplay between PTPs and PTKs in cell signaling. conditions. Considerable progress has been made in the determination of the chromosomal localization of genes encoding PTPs, with the aim of correlating map positions with sites of abnormality in human disease states. New and tantalizing results are being reported frequently. Most notable is the gene for PTP~/on chromosome 3p21, a segment frequently altered in renal and smallcell lung carcinomas. It now appears that mutations may occur in the extracellular segment of PTP~/and thus may create a receptor-like PTP that can no longer respond to its external signals 2. Several studies have reported the inhibitory effects of PTPs on cellular transformation in tissue culture systems. Expression of PTPIB has been shown to block transformation mediated by Neu 3 and partially revert transformation by Src 4, both of which are oncogenic PTKs. Expression of a closely related phosphatase, TCPTP, has been shown to reverse partially the morphological phenotype of cells transformed by Fins, a deregulated colonystimulating factor receptor s. At least in the case of TCPTP, the reversion of tram Eormation has been found to be accolnpanied by the disappearance of a subset of tyrosyl-phosphorylated proteins, indicating a degree of substrate specificity for the PTP in vivo. The targets of PTPs may be PTKs themselves or the substrates of PTKs (Fig. 1). While more comprehensive studies are needed to define the substrates critical for the transformed phenotype, the results to date convey the idea that PTPs may be powerful antagonists of the actions of normal cellular and oncogenic PTKs. More recently, a growth-suppressor function for a cytoplasmic PTP has been characterized, illustrating the power of a genetic approach to the elucidation of PTP function. HCP (also known as PTP1C, SH-PTP1 or SHP; for reviews, see Refs 6, 7) is a hemopoieticcell PTP characterized by two Src homology 2 (SH2) domains in its aminoterminal segment. SH2 domains have been shown to bind phosphotyrosyl residues in defined primary sequences s. Mutations in the gene encoding HCP that result in aberrant splicing of its