期刊
IUBMB LIFE
卷 63, 期 6, 页码 403-411出版社
WILEY
DOI: 10.1002/iub.442
关键词
G-protein mediated signaling; membrane proteins; serine proteases; glycobiology; signal transduction; signaling
资金
- National Institutes of Health [HL073328, GM090689]
- UC
Protease-activated receptors (PARs) are a unique family of G-protein-coupled receptors (GPCRs) that are irreversibly activated following proteolytic cleavage of their extracellular N-terminus. PARs play critical functions in hemostasis, thrombosis, inflammation, embryonic development, and cancer progression. Because of the irreversible proteolytic nature of PAR activation, signaling by the receptors is tightly regulated. Three distinct processes including desensitization, internalization, and lysosomal degradation, regulate the temporal and spatial aspects of activated PAR signaling. Post-translational modifications play a critical role in regulating each of these processes and here we review the nature of PAR post-translational modifications and their importance in signal regulation. The PARs are activated by numerous proteases, and some can elicit distinct cellular responses, how this biased agonism is determined is unknown. Further study of the function of post-translational modifications of the PARs will lead to a greater understanding of the physiological regulation of baised agonism and how PAR signaling is precisely controlled in different cellular contexts. (C) 2011 IUBMB IUBMB Life, 63(6): 403-411, 2011
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