A HUMAN TRANSMEMBRANE PROTEIN-TYROSINE-PHOSPHATASE, PTP-ZETA, IS EXPRESSED IN BRAIN AND HAS AN N-TERMINAL RECEPTOR DOMAIN HOMOLOGOUS TO CARBONIC-ANHYDRASES
A HUMAN TRANSMEMBRANE PROTEIN-TYROSINE-PHOSPHATASE, PTP-ZETA, IS EXPRESSED IN BRAIN AND HAS AN N-TERMINAL RECEPTOR DOMAIN HOMOLOGOUS TO CARBONIC-ANHYDRASES
复制标题
DOI：
10.1073/pnas.89.16.7417
复制
发表时间：
1992-08-15
影响因子：
11.1
通讯作者：
SAITO, H
中科院分区：
文献类型：
--
作者：
KRUEGER, NX;SAITO, H
蛋白质酪氨酸磷酸酶（PTPases，EC 3.1.3.48）在蛋白质酪氨酸磷酸化的调节中起关键作用。最近，人们发现，PTK基因家族表现出大量的各种不同的功能域与PTK催化结构域。在本文中，我们报告了完整的cDNA序列的人跨膜PTP-zeta，从胎脑cDNA文库中分离。推导的人PTP-zeta的氨基酸序列由19个氨基酸的推定信号肽、1616个氨基酸的非常大的胞外结构域、26个氨基酸的跨膜肽和653个氨基酸的胞质结构域组成。人PTP-ζ的细胞外部分含有两个显著的结构特征：与碳酸酐酶（碳酸氢裂解酶，EC 4.2.1.1）同源的N-末端280个氨基酸序列，以及没有半胱氨酸残基的1048个氨基酸的序列。虽然PTP-zeta的碳酸酐酶样结构域不太可能具有任何碳酸酐酶活性，但其三维结构可能与碳酸酐酶的三维结构非常相似，这是一种结合小的可溶性配体的理想结构。人PTP-zeta的胞质部分含有两个重复的PTPase-like结构域，当在大肠杆菌中表达时，其在体外具有PTPase-like活性。突变分析表明，只有膜近端的PTK结构域是催化活性的。逆转录-聚合酶链反应分析表明，人PTP-zeta在胶质母细胞瘤细胞系中高度表达。
Protein-tyrosine-phosphatases (PTPases, EC 3.1.3.48) play a crucial role in the regulation of protein tyrosine phosphorylation. Recently, it was found that the PTPase gene family exhibits a large variety of different functional domains associated with the PTPase catalytic domains. In this paper, we report the complete cDNA sequence of a human transmembrane PTPase, PTP-zeta, isolated from fetal brain cDNA libraries. The deduced amino acid sequence of human PTP-zeta is composed of a putative signal peptide of 19 amino acids, a very large extracellular domain of 1616 amino acids, a transmembrane peptide of 26 amino acids, and a cytoplasmic domain of 653 amino acids. The extracellular portion of human PTP-zeta contains two striking structural features: the N-terminal 280-amino acid sequence that is homologous to carbonic anhydrases (carbonate hydro-lyase, EC 4.2.1.1), and a sequence of 1048 amino acids without a cysteine residue. While it is unlikely that the carbonic anhydrase-like domain of PTP-zeta has any carbonic anhydrase activity, its three-dimensional structure may be quite similar to that of carbonic anhydrases, a structure that appears ideal for binding a small soluble ligand. The cytoplasmic portion of human PTP-zeta contains two repeated PTPase-like domains, which, when expressed in Escherichia coli, had PTPase activity in vitro. Mutational analyses indicate that only the membrane-proximal PTPase domain is catalytically active. Reverse transcription-polymerase chain reaction analyses indicate that human PTP-zeta is highly expressed in a glioblastoma cell line.