NDLI: Thrombin-mediated proteoglycan synthesis utilizes both protein-tyrosine kinase and serine/threonine kinase receptor transactivation in vascular smooth muscle cells.

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Thrombin-mediated proteoglycan synthesis utilizes both protein-tyrosine kinase and serine/threonine kinase receptor transactivation in vascular smooth muscle cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Febbraio, Mark A. Burch, Micah L. Osman, Narin Getachew, Robel Little, Peter J.
Description	Author Affiliation: Burch ML ( Diabetes Complications Laboratory, Royal Melbourne Institute of Technology University, Bundoora, Victoria 3004, Australia.)
Abstract	G protein-coupled receptor signaling is mediated by three main mechanisms of action; these are the classical pathway, ß-arrestin scaffold signaling, and the transactivation of protein-tyrosine kinase receptors such as those for EGF and PDGF. Recently, it has been demonstrated that G protein-coupled receptors can also mediate signals via transactivation of serine/threonine kinase receptors, most notably the transforming growth factor-ß receptor family. Atherosclerosis is characterized by the development of lipid-laden plaques in blood vessel walls. Initiation of plaque development occurs via low density lipoprotein retention in the neointima of vessels due to binding with modified proteoglycans secreted by vascular smooth muscle cells. Here we show that transactivation of protein-tyrosine kinase receptors is mediated by matrix metalloproteinase triple membrane bypass signaling. In contrast, serine/threonine kinase receptor transactivation is mediated by a cytoskeletal rearrangement-Rho kinase-integrin system, and both protein-tyrosine kinase and serine/threonine kinase receptor transactivation concomitantly account for the total proteoglycan synthesis stimulated by thrombin in vascular smooth muscle. This work provides evidence of thrombin-mediated proteoglycan synthesis and paves the way for a potential therapeutic target for plaque development and atherosclerosis.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	10
Volume Number	288
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2013-03-08
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Myocytes, Smooth Muscle Drug Effects Protein-Serine-Threonine Kinases Metabolism Protein-Tyrosine Kinases Proteoglycans Biosynthesis Thrombin Pharmacology Blotting, Western Cells, Cultured Cytoskeleton Hemostatics Integrins Matrix Metalloproteinases Microscopy, Confocal Muscle, Smooth, Vascular Cytology Phosphorylation Genetics Receptors, G-Protein-Coupled Receptors, Transforming Growth Factor Beta Serine Smad2 Protein Transcriptional Activation Transforming Growth Factor Beta Rho-Associated Kinases Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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