alexa Therapeutic implications of endothelin and thrombin G-protein-coupled receptor transactivation of tyrosine and serine threonine kinase cell surface receptors.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Clinical & Experimental Pharmacology

Author(s): Kamato D, Burch ML, Osman N, Zheng W, Little PJ

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Abstract OBJECTIVES: This review discusses the latest developments in G protein coupled receptor (GPCR) signalling related to the transactivation of cell surface protein kinase receptors and the therapeutic implications. KEY FINDINGS: Multiple GPCRs have been known to transactivate protein tyrosine kinase receptors for almost two decades. More recently it has been discovered that GPCRs can also transactivate protein serine/threonine kinase receptors such as that for transforming growth factor (TGF)-β. Using the model of proteoglycan synthesis and glycosaminoglycan elongation in human vascular smooth muscle cells which is a component of an in vitro model of atherosclerosis, the dual tyrosine and serine/threonine kinase receptor transactivation pathways appear to account for all of the response to the agonists, endothelin and thrombin. SUMMARY: The broadening of the paradigm of GPCR receptor transactivation explains the broad range of activities of these receptors and also the efficacy of GPCR antagonists in cardiovascular therapeutics. Deciphering the mechanisms of transactivation with the aim of identifying a common therapeutic target remains the next challenge. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society. This article was published in J Pharm Pharmacol and referenced in Journal of Clinical & Experimental Pharmacology

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