LEPR

Synonyms

CD295, OB receptor, LEPR, HuB219, DB, Leptin Receptor, LEP-R, OB-R, OBR, CD295 Antigen, LEPRD, Receptors, Leptin

Description

LEPR is a receptor for hormone LEP/leptin. On ligand binding, mediates LEP central and peripheral effects through the activation of different signaling pathways such as JAK2/STAT3 and MAPK cascade/FOS. In the hypothalamus, LEP acts as an appetite-regulating factor that induces a decrease in food intake and an increase in energy consumption by inducing anorexinogenic factors and suppressing orexigenic neuropeptides, also regulates bone mass and secretion of hypothalamo-pituitary-adrenal hormones . In the periphery, increases basal metabolism, influences reproductive function, regulates pancreatic beta-cell function and insulin secretion, is pro-angiogenic and affects innate and adaptive immunity. Control of energy homeostasis and melanocortin production (stimulation of POMC and full repression of AgRP transcription) is mediated by STAT3 signaling, whereas distinct signals regulate NPY and the control of fertility, growth and glucose homeostasis. Involved in the regulation of counter-regulatory response to hypoglycemia by inhibiting neurons of the parabrachial nucleus. Has a specific effect on T lymphocyte responses, differentially regulating the proliferation of naive and memory T -ells. Leptin increases Th1 and suppresses Th2 cytokine production.May transport LEP across the blood-brain barrier. Binds LEP and mediates LEP endocytosis. Does not induce phosphorylation of and activate STAT3.Antagonizes Isoform A and isoform B-mediated LEP binding and endocytosis.

KO Status

F0

Drug Information

Launched drug: 1
Drug in clinical trials: 1
Latest Research Phase: Approved

Drug Name

Code

Phase

Company

Indications

Clinical Trials

Metreleptin

AC-164594, KTR-103

Approved

Amylin Pharmaceutical, Bristol-Myers Squibb Company, Astrazeneca Plc

Lipodystrophy, Lipodystrophy, Familial Partial

REGN-4461

REGN-4461

Phase 2 Clinical

Regeneron Pharmaceuticals Inc

Lipodystrophy, Lipodystrophy, Congenital Generalized

ARV-1802

ARV-1802

Preclinical

Arrevus

Neoplasms

Metreleptin/Pramlintide Acetate

AC-137-164594

Discontinued

Amylin Pharmaceutical

Obesity

References


Title

Authors

Source

Enhancing leptin response by preventing SH2-containing phosphatase 2 interaction with Ob receptor

Carpenter L.R., Farruggella T.J., Symes A., Karow M.L., Yancopoulos G.D., Stahl N.,

Proc. Natl. Acad. Sci. U.S.A. 95:6061-6066(1998)

Human leptin receptor. Determination of disulfide structure and N-glycosylation sites of the extracellular domain

Haniu M., Arakawa T., Bures E.J., Young Y., Hui J.O., Rohde M.F., Welcher A.A., Horan T.,

J. Biol. Chem. 273:28691-28699(1998)

Leptin secretion and leptin receptor in the human stomach

Sobhani I., Bado A., Vissuzaine C., Buyse M., Kermorgant S., Laigneau J.P., Attoub S., Lehy T., Henin D., Mignon M., Lewin M.J.,

Gut 47:178-183(2000)

Expression of leptin receptors and response to leptin stimulation of human natural killer cell lines

Zhao Y., Sun R., You L., Gao C., Tian Z.,

Biochem. Biophys. Res. Commun. 300:247-252(2003)

Leptin expression in human primary skeletal muscle cells is reduced during differentiation

Solberg R., Aas V., Thoresen G.H., Kase E.T., Drevon C.A., Rustan A.C., Reseland J.E.,

J. Cell. Biochem. 96:89-96(2005)

Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry

Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.,

J. Proteome Res. 4:2070-2080(2005)

Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry

Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.,

J. Proteome Res. 8:651-661(2009)

20 years of leptin: connecting leptin signaling to biological function

Allison M.B., Myers M.G. Jr.,

J. Endocrinol. 223:T25-T35(2014)

An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome

Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.,

J. Proteomics 96:253-262(2014)

Leptin modulates autophagy in human CD4+CD25- conventional T cells

Cassano S., Pucino V., La Rocca C., Procaccini C., De Rosa V., Marone G., Matarese G.,

Metabolism 63:1272-1279(2014)