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Figure 3 | Cell Communication and Signaling

Figure 3

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

Figure 3

Concepts and mechanisms of PAR receptor crosstalk with other receptors and signal transducers. PAR receptor crosstalk involves (A) transactivation of receptor tyrosine kinases (RTKs) and receptor serine/threonine kinases (RSTKs), (B) PAR-PAR receptor interactions, and (C) PAR interplay with other non-PAR GPCRs and non-PAR signal transducers. (A) PARs can mediate transactivation of RTKs by an immediate matrix metalloproteinase (MMP)-catalysed release of RTK agonists from the cell surface, e.g. heparin-binding EGF, or transforming growth factor (TGF)-α, that in turn stimulates RTK signalling. PARs are also able to mediate transactivation of RSTKs by mechanisms including integrin-mediated activation of latent TGF-β. In addition, PARs can induce RTK transactivation via intracellular mechanisms including activation of Src, generation of reactive oxygen species (ROS), and inhibition of protein tyrosine phosphatases (PTPs). (B) PAR-PAR crosstalk involves PAR homo- and heterodimerization and PAR-PAR trans-signalling. (C) PARs are able to mediate transactivation of other non-GPCRs via extracellular release of GPCR agonists (e.g. the prostaglandin receptor by release of prostaglandins) and by intracellular mechanisms on the signalling (bradykinin B2 receptor, purinergic ADP receptor), gene transcription (angiotensin receptor subtype 1, serotonin receptor subtype 2), and receptor trafficking level. PARs further communicate with non-PAR signal transducers at both the signalling (toll-like receptors, ion channel receptors, NOD-like receptors) and receptor trafficking level (cargo receptors p23 and p24A).

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