TABLE 3

PARs: Nomenclature, receptor-activating or disarming proteinases, agonists/antagonists and signaling pathways

The table lists the four PARs according to their gene nomenclature, along with the PAR-regulating enzymes, PAR agonists, PAR antagonists, radioligand binding probes, and the G proteins that the PARs activate.

Receptor	Gene	Agonist Proteinases	Agonist Peptide	Peptido-Mimetic Agonist	Antagonist or Inhibiting Proteinases	Radioligand	G Protein
PAR1	F2R (Hs), F2r(Mm), F2r(Rn)	Thrombin (Vu et al., 1991)	TFLLR-NH₂	None	Vorapaxar (Chackalamannil et al., 2005, 2008), Atopaxar (Kogushi et al., 2011), RWJ56110 (Andrade-Gordon et al., 1999) KLK4 possible disarming (Ramsay et al., 2008)	[³H]haTRAP (Ahn et al., 1997)	Gq/11, Gi/o, G12/13
		Riewald et al., 2001; Riewald and Ruf, 2001			KLK8 disarming (Ramachandran et al., 2012a)
		Activated protein C (Riewald et al., 2002, 2003), Plasmin (Kimura et al., 1996; Kuliopulos et al., 1999)			KLK14 disarming (Oikonomopoulou et al., 2006a,b)
		Gingipains-R (RgpB and HrgpA; arginine-specific cysteine proteinases) (Lourbakos et al., 2001a,b), MMP1 (Boire et al., 2005; Trivedi et al., 2009), MMP13 (Jaffre et al., 2012), Neutrophil Elastase (Mihara et al., 2013), Cathepsin-G (Molino et al., 1995)
		KLK4 (Ramsay et al., 2008; Mize et al., 2008; Wang et al., 2010)
		KLK6 (Vandell et al., 2008)
		KLK14 (Oikonomopoulou et al., 2006a,b)
PAR2	F2RL1 (Hs), F2rl1(Mm), F2rl1(Rn)	Trypsin (Nystedt et al., 1994, 1995a,b; Bohm et al., 1996a; Saifeddine et al., 1996)	2f-LIGRLO-NH₂ (McGuire et al., 2004), SLIGRL-NH₂, SLIGKV-NH₂	GB110 (Barry et al., 2010), AC-55541 and AC-264613; (Gardell et al., 2008)	GB88 (Suen et al., 2012); P2pal18S pepducin (Sevigny et al., 2011)	2-furoyl-LIGRL[N[3H]propionyl]-O-NH₂ (Hollenberg et al., 2008), [3H]2-furoyl-LIGRL-NH₂ (Kanke et al., 2005)	Gq/11, Gi/o, G12/13
		Trypsin IV (Cottrell et al., 2004), Tryptase (Mirza et al., 1997; Molino et al., 1997)
		Tissue factor-Factor VIIa-Xa (Camerer et al., 2000), Membrane-type serine protease 1 (Takeuchi et al., 2000)
		Acrosin (Smith et al., 2000)
		Dust mite proteinases Der P3 and Der P9 (Sun et al., 2001)
		Gingipains-R (RgpB and HrgpA; arginine-specific cysteine proteinases (Lourbakos et al., 1998)
		Cockroach proteases (Arizmendi et al., 2011; Page et al., 2010), Neutrophil Elastase (Ramachandran et al., 2011)
		KLK2 (Mize et al., 2008)
		KLK4 (Ramsay et al., 2008; Mize et al., 2008)
		KLK5 (Oikonomopoulou et al., 2006a,b; Stefansson et al., 2008; Briot et al., 2009)
		KLK6 (Oikonomopoulou et al., 2006a,b; Vandell et al., 2008)
		KLK14 (Oikonomopoulou et al., 2006a,b; Stefansson et al., 2008; Gratio et al., 2011; Chung et al., 2012; Ramachandran et al., 2012a)
PAR3	F2RL2 (Hs), F2rl2 (Mm), F2rl2 (Rn)	Thrombin (Ishihara et al., 1997)(PAR3 can be cleaved by thrombin, however the ability of this receptor to signal is unclear).	TFRGAP (Bretschneider et al., 2003)(This is the predicted TL derived sequence for thrombin cleaved PAR3. However the signaling properties of this peptide are unclear)(Hansen et al., 2004).	None	None
PAR4	F2RL3 (Hs), F2rl3 (Mm), F2rl3 (Rn)	Thrombin (Kahn et al., 1998; Xu et al., 1998)	AYPGKF-NH₂ (Faruqi et al., 2000; Hollenberg and Saifeddine, 2001).	None	YD-3 (Wu et al., 2002); ML354 (Young et al., 2013; Wen et al., 2014)		Gq/11, Gi/o
		Trypsins (Xu et al., 1998)
		Trypsin IV (Cottrell et al., 2004)
		Cathepsin G (Sambrano et al., 2000)
		Plasmin (Quinton et al., 2004)
		Gingipains-R (RgpB and HrgpA; arginine-specific cysteine proteinases) (Lourbakos et al., 2001b)
		KLK14 (Oikonomopoulou et al., 2006a,b)

PAR, proteinase-activated receptor.