Sui, X. F., Kiser, T. D., Hyun, S. W., Angelini, D. J., Del Vecchio, R. L., Young, B. A., Hasday, J. D., Romer, L. H., Passaniti, A., Tonks, N. K., Goldblum, S. E. (April 2005) Receptor protein tyrosine phosphatase mu regulates the paracellular pathway in human lung microvascular endothelia. American Journal of Pathology, 166 (4). pp. 1247-1258. ISSN 0002-9440
Abstract
The pulmonary vascular endothelial paracellular pathway and zonula adherens (ZA) integrity are regulated, in part, through protein tyrosine phosphorylation. ZA-associated protein tyrosine phosphatase (PTP)s are thought to counterregulate tyrosine phosphorylation events within the ZA multiprotein complex. One such receptor PTP, PTP mu, is highly expressed in lung tissue and is almost exclusively restricted to the endothelium. We therefore studied whether PTP mu, in pulmonary vascular endothelia, associates with and/or regulates both the tyrosine phosphorylation state of vascular endothelial (VE)cadherin and the paracellular pathway. PTP mu was expressed in postconfluent human pulmonary artery and lung microvascular endothelial cells (ECs) where it was almost exclusively restricted to EG-EC boundaries. In human lung microvascular ECs, knockdown of PTP mu through RNA interference dramatically impaired barrier function. In immortalized human microvascular ECs, overexpression of wild-type PTP mu enhanced barrier function. PTP mu-VE-cadherin interactions were demonstrated through reciprocal co-immunoprecipitation assays and co-localization with double-label fluorescence microscopy. When glutathione S-transferase-PTP mu was incubated with purified recombinant VE-cadherin, and when glutathione S-transferase-VE-cadherin was incubated with purified recombinant PTP mu, PTP mu directly bound to VE-cadherin. Overexpression of wild-type PTP mu decreased tyrosine phosphorylation of VE-cadherin. Therefore, PTP mu is expressed in human pulmonary vascular endothelia where it directly binds to VE-cadherin and regulates both the tyrosine phosphorylation. state of VE-cadherin and barrier integrity.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | adherens junction proteins cadherin catenin complex cadherin_catenin complex PTP-mu n-cadherin in-vivo RTPT-mu monolayer integrity cytoplasmic domain homophylic binding neurite outgrowth |
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > protein tyrosine phosphatase |
| CSHL Authors: | |
| Communities: | CSHL labs > Tonks lab |
| Depositing User: | CSHL Librarian |
| Date: | April 2005 |
| Date Deposited: | 05 Jan 2012 15:06 |
| Last Modified: | 21 Feb 2017 20:43 |
| PMCID: | PMC1602370 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/22718 |
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