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. Author manuscript; available in PMC: 2022 Jun 1.
Published in final edited form as: J Cardiovasc Pharmacol. 2021 Jun 1;77(6):707–717. doi: 10.1097/FJC.0000000000001013

Figure 1: 12(S)-HETE/GPR31 Signaling Pathways.

Figure 1:

The 12(S)-HETE receptor (GPR31) is Gαi/o coupled and inhibits adenylate cyclase from converting ATP to cAMP. This action causes the reassociation of the regulatory subunits of PKA to its catalytic subunits, inhibiting the kinase activity of PKA. RAF, a member of the MAPK pathway, is capable of being inhibited through phosphorylation by PKA. RAF has been shown to phosphorylate MEK which subsequently activates ERK1/2 which can translocate to the nucleus and promotes gene expression through the activation of nuclear transcription factors. Additionally, RAF has also been shown to induce NF-кB through MEKK1 which also promotes gene expression. Additionally, through alterations of RAF activity, 12(S)-HETE acting on GPR31 may also exert an inhibitory effect on ROCK and MYPT1 related signaling. Lastly, the Gβγ effects of GPCRs like GPR31 have been demonstrated to influence intracellular calcium levels as well as drive PI3K/AKT signaling pathways with downstream consequences to alter gene expression. It is still unknown how the pairing of 12(S)-HETE and GPR31 alters the activation of the large conductance K channels (BKCa).