LEPR
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. Isoform A: May transport LEP across the blood-brain barrier. Binds LEP and mediates LEP endocytosis. Does not induce phosphorylation of and activate STAT3. Isoform E: Antagonizes Isoform A and isoform B-mediated LEP binding and endocytosis. Belongs to the type I cytokine receptor family. Type 2 subfamily. Isoform A is expressed in fetal liver and in hematopoietic tissues and choroid plexus. In adults highest expression in heart, liver, small intestine, prostate and ovary. Low level in lung and kidney. Isoform B is highly expressed in hypothalamus, but also in skeletal muscle. Detected in fundic and antral epithelial cells of the gastric mucosa (PubMed:19159218). Isoform B and isoform A are expressed by NK cells (at protein level) (PubMed:12504075). 5 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: Membrane protein, integral; Receptor, cytokine
Biological Process: angiogenesis; bone growth; cell surface receptor signaling pathway; cholesterol metabolic process; cytokine-mediated signaling pathway; energy homeostasis; energy reserve metabolic process; glial cell proliferation; gluconeogenesis; glucose homeostasis; glycogen metabolic process; leptin-mediated signaling pathway; multicellular organism development; negative regulation of autophagy; negative regulation of gluconeogenesis; negative regulation of hydrolase activity; phagocytosis; positive regulation of cold-induced thermogenesis; positive regulation of protein phosphorylation; regulation of bone remodeling; regulation of feeding behavior; regulation of transport; response to leptin; sexual reproduction; T cell differentiation; transport across blood-brain barrier
