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. 2021 Feb 10;12:632886. doi: 10.3389/fphys.2021.632886

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Copyright © 2021 Hu, Wang, Zhang, Sun and Chen.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Apelin-associated signaling pathways. Apelin-13 (in addition to apelin-17, apelin-36, and [pyr¹]-apelin-13) binds to APJ to couple Gαi, inhibits forskolin (FSK)-induced cAMP generation, and blocks various biological effects produced by the protein kinase A (PKA) pathway; it (or apelin-36) binds to APJ-coupled Gio or Gq/11 to activate extracellular signal-regulated kinase 1/2 (ERK1/2) through protein kinase C (PKC) pathway; it (or [pyr¹]-apelin-13) activates phosphorylation of ribosomal protein S6 kinase (p70S6) through the PI3K/Akt and ERK1/2 signaling pathways. Apelin-13 promotes cell proliferation, division, migration, and metabolic function through the PI3K/Akt signaling pathway or MAPK pathway; and it (or apelin-12) stimulates endothelial nitric oxide synthase (eNOS) through the protein kinase B (PKB) pathway.