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The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state (PubMed:12359238). Signaling by an activated GPCR promotes GDP release and GTP binding (PubMed:29925945). Examples of interacting GPCRs include the adenosine A1 receptor/ADORA1, CNR1, and FPR2 (PubMed:29925945, PubMed:35637350, PubMed:35365641). The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal. Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins (PubMed:12359238). Signaling is mediated via effector proteins, such as adenylate cyclase: inhibits adenylate cyclase activity of ADCY1, ADCY5 and ADCY6, leading to decreased intracellular cAMP levels. Plays an important role in the activation of the transcription factor NFAT in endothelial cells to promote angiogenesis (PubMed:38505600). The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. 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