Proteolytic processing of the protein tyrosine phosphatase 伪 extracellular domain is mediated by ADAM17/TACE

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• 作者：Katja Kapp¹ ; ² ; Jan Siemens¹ ; ³ ; Hans-Ulrich H&auml ; ring ; Reiner Lammers ; ^{reiner.lammers@med.uni-tuebingen.de}
• 关键词：Receptor protein tyrosine phosphatase ; Proteolytic processing ; TACE ; ADAM17 ; Ectodomain cleavage
• 刊名：European Journal of Cell Biology
• 出版年：2012
• 期刊代码：15_01719335
• 类别：bio
• 出版时间：September, 2012
• 卷：91
• 期：9
• 页码：687-693
• 文件大小：704 K

摘要

The receptor protein tyrosine phosphatase alpha (PTP伪) is involved in the regulation of tyrosine kinases like the Src kinase and the insulin receptor. As with other PTPs, its function is determined by alternative splicing, dimerisation, phosphorylation and proteolytical processing. PTP伪 is cleaved by calpain in its intracellular domain, which decreases its potential to dephosphorylate Src kinase. Here, we demonstrate that PTP伪 is also processed in the extracellular domain. Extracellular processing was exclusively found for a splice variant containing an extra nine amino acid insert three residues amino-terminal from the transmembrane domain. Processing was sensitive to the metalloprotease-inhibitor Batimastat, and CHO-M2 cells lacking a disintegrin and metalloproteinase 17 (ADAM17; tumor-necrosis-factor 伪 converting enzyme) activity were not able to cleave PTP伪. After transient overexpression of ADAM17 and PTP伪 in these cells, processing was restored, proving that ADAM17 is involved in this process. Further characterization of the consequences of processing revealed that dephosphorylation of the insulin receptor or activation of Src was not affected but focus formation was reduced. We conclude that extracellular proteolytic processing is a novel mechanism for PTP伪 regulation.