STRUCTURE OF LOW MOLECULAR WEIGHT TYROSINE PHOSPHATASES

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。PTPCaaX-1(PRL-1)是一种新的磷酸酶，与肿瘤细胞的转移密切相关。像所有蛋白酪氨酸磷酸酶一样，这些酶含有保守的活性部位基序(CX5R)。这些磷酸酶所特有的是核定位序列和法尼化所需的C-末端CAAX盒基序。序列比较表明，PRL蛋白与CDC14和PTEN最相似，每种蛋白有大约25%的同源性。然而，这种相似性仅限于活性部位周围约70个残基的区域，这表明PRL酶构成了一个新的磷酸酶家族。到目前为止，PRL家族的任何成员都没有可用的结构信息。从高分辨率的溶液状态结构中获得的详细信息最终可能被证明在打破这些酶的过度表达与转移之间的联系方面有价值。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. PTPCaaX-1 (PRL-1) represents a novel class of phosphatase, which has been implicated in triggering metastasis of cancerous cells. Like all protein tyrosine phosphatases, these enzymes contain the conserved active site motif (CX5R). Unique to these phosphatases is a nuclear localization sequence and the C-terminal CaaX box motif required for farnesylation. Sequence comparisons show the PRL proteins to be most similar to cdc14 and PTEN, sharing approximately 25% identity with each. However, this similarity is limited to a region of approximately 70 residues surrounding the active site, suggesting that the PRL enzymes constitute a new family of phosphatase. To date no structural information is available for any member of the PRL family. The detailed information obtained from a high-resolution, solution-state structure could ultimately prove valuable in breaking the link between overexpression of these enzymes and metastasis.