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Leptin receptor functions: When leptin binds to its receptor (LEPR-B) the receptor undergoes a conformational change that activates the receptor-associated.

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Presentation on theme: "Leptin receptor functions: When leptin binds to its receptor (LEPR-B) the receptor undergoes a conformational change that activates the receptor-associated."— Presentation transcript:

1 Leptin receptor functions: When leptin binds to its receptor (LEPR-B) the receptor undergoes a conformational change that activates the receptor-associated Jak2 tyrosine kinase. Activated Jak2 will autophosphrylate itself as well as phosphorylate the tyrosine (Y) residues in LEPR-B at positions 985, 1077, and Phosphorylated Y-985 serves as a docking site for SHP2 (SH2 domain containing protein tyrosine phosphatase, also called PTP1D). The gene that encodes SHP2 is identified as PTPN11. Phosphorylated Y-1077 serves as a docking site for STAT5 (signal transduction and activation of transcription 5). Phosphorylated Y-1138 serves as a docking site for STAT3. When SHP2, STAT5, and STAT3 bind to phosphorylated LEPR-B, they themselves are activated by Jak2-mediated phosphorylation. Activated SHP2 in turn activates GRB2 (growth factor receptor-bound protein 2) which then activates the ERK1/2 (extracellular-regulated kinase 1/2) signal pathway that results in increased transcription of the EGR-1 (early growth response protein 1) gene. Activated STAT3 in turn activates the transcription of SOCS3 (suppressor of cytokine signaling 3). SOCS3 will then interact with Y-985 and attenuate signaling from SHP2 as well as interact with Jak2 and attenuate its tyrosine kinase activity resulting in a negative feedback loop. Reproduced with permission of the medical biochemistry page, LLC. Source: Adipose Tissue and Obesity: Associated Metabolic Disturbances, Integrative Medical Biochemistry Examination and Board Review Citation: King MW. Integrative Medical Biochemistry Examination and Board Review; 2014 Available at: Accessed: November 13, 2017 Copyright © 2017 McGraw-Hill Education. All rights reserved


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