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  PAR1 Scaffolds TGF beta RII to Downregulate TGF-beta Signaling and Activate ESC Differentiation to Endothelial Cells

Gong, H., An, S., Sassmann, A., Liu, M., Mastej, V., Mittal, M., et al. (2016). PAR1 Scaffolds TGF beta RII to Downregulate TGF-beta Signaling and Activate ESC Differentiation to Endothelial Cells. STEM CELL REPORTS, 7(6), 1050-1058. doi:10.1016/j.stemcr.2016.10.006.

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 Creators:
Gong, Haixia, Author
An, Shejuan, Author
Sassmann, Antonia1, Author              
Liu, Menglin, Author
Mastej, Victoria, Author
Mittal, Manish, Author
Zhang, Wei, Author
Hong, Zhigang, Author
Offermanns, Stefan1, Author              
Rehman, Jalees, Author
Malik, Asrar B., Author
Affiliations:
1Pharmacology, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591696              

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Free keywords: PROTEIN-COUPLED RECEPTORS; HUMAN EMBRYONIC STEM; THROMBIN; PLURIPOTENCY; G-ALPHA(13); MAINTENANCE; MECHANISMS; DISEASES; GPR56Cell Biology;
 Abstract: We studied the function of the G-protein-coupled receptor PAR1 in mediating the differentiation of mouse embryonic stem cells (mESCs) to endothelial cells (ECs) that are capable of inducing neovascularization. We observed that either deletion or activation of PAR1 suppressed mouse embryonic stem cell (mESC) differentiation to ECs and neovascularization in mice. This was mediated by induction of TGF beta RII/TGF beta RI interaction, forming an active complex, which in turn induced SMAD2 phosphorylation. Inhibition of TGF-beta signaling in PAR1-deficient mESCs restored the EC differentiation potential of mESCs. Thus, PAR1 in its inactive unligated state functions as a scaffold for TGF beta RII to downregulate TGF-beta signaling, and thereby promote ESC transition to functional ECs. The PAR1 scaffold function in ESCs is an essential mechanism for dampening TGF-beta signaling and regulating ESC differentiation.

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Language(s): eng - English
 Dates: 2016
 Publication Status: Published in print
 Pages: 9
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Degree: -

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Title: STEM CELL REPORTS
Source Genre: Journal
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Publ. Info: 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA : CELL PRESS
Pages: - Volume / Issue: 7 (6) Sequence Number: - Start / End Page: 1050 - 1058 Identifier: ISSN: 2213-6711