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MRGPRX1, MRGPRX2, MRGPRX4, and MRGPRD can mediate Gaq11-dependent pathways leading to phospholipase C (PLC) driven calcium responses from the endoplasmic reticulum. MRGPRX1, MRGPRX2, and MRGPRD can additionally engage Gai and MRGPRD can recruit Gast that drives cAMP production. In addition to G-proteins, beta-arrestin signaling is engaged by MRGPRs and selectively other cell-surface receptor-like RAMP-2 can inhibit MRGPRX4 expression and basal or agonist-induced activation.

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