THE LAR/PTP-DELTA/PTP-SIGMA SUBFAMILY OF TRANSMEMBRANE PROTEIN-TYROSINE-PHOSPHATASES - MULTIPLE HUMAN LAR, PTP-DELTA, AND PTP-SIGMA ISOFORMS ARE EXPRESSED IN A TISSUE-SPECIFIC MANNER AND ASSOCIATE WITH THE LAR-INTERACTING PROTEIN LIP.1
THE LAR/PTP-DELTA/PTP-SIGMA SUBFAMILY OF TRANSMEMBRANE PROTEIN-TYROSINE-PHOSPHATASES - MULTIPLE HUMAN LAR, PTP-DELTA, AND PTP-SIGMA ISOFORMS ARE EXPRESSED IN A TISSUE-SPECIFIC MANNER AND ASSOCIATE WITH THE LAR-INTERACTING PROTEIN LIP.1
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DOI：
10.1073/pnas.92.25.11686
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发表时间：
1995-12-05
影响因子：
11.1
通讯作者：
STREULI, M
中科院分区：
文献类型：
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作者：
PULIDO, R;SERRAPAGES, C;STREULI, M
跨膜蛋白酪氨酸磷酸酶(PTPase)LAR、PTP Delta和PTP sigma分别含有两个胞内PTPase结构域和一个由Ig样和纤维连接蛋白III型样结构域组成的胞外区域。我们描述了人PTP sigma(HPTP Sigma)的克隆和鉴定，并比较了LAR、HPTP Delta和HPTP sigma的结构、选择性剪接、组织分布和PTPase活性，以及它们与细胞内盘绕的LAR相互作用蛋白LIP.1的结合能力。总体而言，这三种PTPase在结构上非常相似，具有%的氨基酸同源性，LAR、HPTP Delta和HPTP sigma的多种异构体似乎是通过组织特异性的选择性剪接产生的，这些片段编码位于细胞外和细胞内的4-16个氨基酸的多肽。这些多肽的替代用途取决于所分析的组织信使核糖核酸。HPTP sigma和HPTP Delta的短亚型也被检测到，它们只包含8个纤维连接蛋白III型样结构域中的4个。Northern印迹分析表明，LAR和HPTP sigma广泛分布，而HPTP Delta的表达在很大程度上仅限于大脑，只包含四个纤维连接蛋白III样结构域的短HPTP sigma亚型也是如此，LAR、HPTP Delta和HPTP sigma在体外显示出相似的PTPase活性，并且这三种蛋白都与LIP.1相互作用，LIP.1被认为可以将LAR招募到局灶性粘连中，因此，这些密切相关的PTPase MAg在不同的组织中发挥着相似的功能。
The transmembrane protein-tyrosine-phosphatases (PTPases) LAR, PTP delta, and PTP sigma each contain two intracellular PTPase domains and an extracellular region consisting of Ig-like and fibronectin type III-like domains, We describe the cloning and characterization of human PTP sigma (HPTP sigma) and compare the structure, alternative splicing, tissue distribution, and PTPase activity of LAR, HPTP delta, and HPTP sigma, as well their ability to associate with the intracellular coiled-coil LAR-interacting protein LIP.1. Overall, these three PTPases are structurally very similar, sharing 64% amino acid identity, Multiple isoforms of LAR, HPTP delta, and HPTP sigma appear to be generated by tissue-specific alternative splicing of up to four mini-exon segments that encode peptides of 4-16 aa located in both the extracellular and intracellular regions. Alternative usage of these peptides varies depending on the tissue mRNA analyzed. Short isoforms of both HPTP sigma and HPTP delta were also detected that contain only four of the eight fibronectin type III-like domains. Northern blot analysis indicates that LAR and HPTP sigma are broadly distributed whereas HPTP delta expression is largely restricted to brain, as is the short HPTP sigma isoform containing only four fibronectin type III-like domains, LAR, HPTP delta, and HPTP sigma exhibit similar in vitro PTPase activities and all three interact with LIP.1, which has been postulated to recruit LAR to focal adhesions, Thus, these closely related PTPases mag perform similar functions in various tissues.