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Figure 1 | Cell Communication and Signaling

Figure 1

From: Proteinase-activated receptors (PARs) – focus on receptor-receptor-interactions and their physiological and pathophysiological impact

Figure 1

Model for activation of PAR 1. The scheme illustrates activation of the intact receptor by distinct mechanisms involving either proteolysis (left) or a synthetic PAR1-activating peptide (right): (A) proteolysis unmasks a tethered receptor-activating ligand (TL) sequence. The classical ‘canonical’ PAR1 TL sequence generated by thrombin is: SFLLRN--- [10]. Distinct ‘non-canonical’ receptor-activating TL sequences are also generated by neutrophil proteinase-3 (PR3: TLDPR---) [11], matrix metalloproteinase-1 (MMP1: PRSFLL---) [12, 13], neutrophil elastase (NE: RNPNDK---) [11], and activated protein-C (APC: NPNDK---) [14, 15]. The different proteinase-revealed TLs can drive very distinct signal pathways (distinct coloured arrows for PAR1 response at the bottom). (B) synthetic peptides with sequences that mimic the tethered ligand (e.g. TFLLRN-NH2 for PAR1) can activate PAR signalling without the need for receptor proteolysis. Peptides derived from the different enzyme-revealed tethered ligand sequences can stimulate ‘biased signaling’. (Illustration modified with permission from Hollenberg & Compton, Ref. [2]).

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