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. 2019 May 28;20(11):2622. doi: 10.3390/ijms20112622

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© 2019 by the author.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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Leptin receptor signaling is mediated by JAK-STAT, PI3K-Akt, and SHP2-ERK pathway. Leptin binds to ObRb and activates JAK2, and induced to the phosphorylation of Tyr985, Tyr1077, and Tyr1138 of ObRb. PY-985, PY-1077, and PY-1138 bind to their downstream molecules and proceeds to phosphorylation of JAK2-STAT3, JAk2-STAT5, PI3K-IRS-Akt, SHP2-ERK pathways. These signaling are negatively regulated by SOCS3. Dysregulation of the leptin receptor signaling is involved in the onset of leptin resistance, inflammation and cancer.