Sphingosine-1-Phosphate and Its Receptors: A Mutual Link between Blood Coagulation and Inflammation

Table 1

Mechanistic studies which directly link S1P and its receptors to the thrombin or FXa receptors PAR-1 to PAR-4, their (patho)physiological actions, and associated signaling pathways.

Receptor(s)/stimuli	G-protein binding	Signaling pathway	Physiological action(s)	Reference
S1P/thrombin	Not described	NF-B,  EGR-1/ERK1/2	Enhanced tissue factor expression in endothelial cells	[59]
S1P/thrombin	GIT1 and GIT2	Focal adhesion kinase (FAK)/Src	Regulation of endothelial barrier function	[46]
S1PR3/PAR-1; (via SphK1)	G	IL-1B	Induces tissue factor production, inflammation, and coagulation	[37]
S1PR1 and S1PR3/PAR-1	G; G	Rac-1/Rho	Inflammatory responses	[76]
S1P/PAR-1; (via SphK1)	G	NF-B	Regulation of endothelial function	[75]
SphK1/FXa via; PAR-1 and PAR-2	Gq	Rho-kinase, PKC	Mitogenesis and migration of VSMCs	[79]
S1P/FXa	Gα; G	Rho-A/GTPases	Proliferation/survival	[80]
S1PR3/PAR-4	G	Akt,  p38 MAPK	Migration, chemotaxis	[107]