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

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Item Type:	Article
Title:	Proteolytic processing of the protein tyrosine phosphatase alpha extracellular domain is mediated by ADAM17/TACE
Creators Name:	Kapp, K., Siemens, J., Haering, H.U. and Lammers, R.
Abstract:	The receptor protein tyrosine phosphatase alpha (PTP alpha) 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. PTPα is cleaved by calpain in its intracellular domain, which decreases its potential to dephosphorylate Src kinase. Here, we demonstrate that PTP alpha 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 alpha converting enzyme) activity were not able to cleave PTP alpha. After transient overexpression of ADAM17 and PTP alpha 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 PTPα regulation.
Keywords:	Receptor Protein Tyrosine Phosphatase, Proteolytic Processing, TACE, ADAM17, Ectodomain Cleavage, Animals, Mice
Source:	European Journal of Cell Biology
ISSN:	0171-9335
Publisher:	Elsevier / Urban & Fischer
Volume:	91
Number:	9
Page Range:	687-693
Date:	September 2012
Official Publication:	https://doi.org/10.1016/j.ejcb.2012.04.003
PubMed:	View item in PubMed

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