leptin receptor; LEP-R; OB receptor; OB-R; HuB219; CD295 (LEPR, DB, OBR)
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Function
- receptor for leptin (obesity factor)
- on ligand binding, mediates signaling through JAK2/STAT3
- role in regulation of fat metabolism &, in a hematopoietic pathway, required for normal lymphopoiesis
- may play a role in reproduction
- able to mediate the ERK/FOS signaling pathway (putative)
- on leptin stimulation, homodimerizes
- on leptin binding, phosphorylated on 2 conserved C-terminal Tyr (isoform B only) by JAK2
- phosphorylated receptor binds a number of SH2 domain- containing proteins including STAT3, PTPN11, & SOCS3 (putative)
- interaction with SOCS3 inhibits LRb signaling (putative)
- Tyr-986 is required for complete binding & activation of PTPN11, ERK/FOS activation &, for interaction with SOCS3 (putative)
- phosphorylation on Tyr-1141 is required for STAT3 binding & activation
Structure
- cytoplasmic domain may be essential for intracellular signal transduction by activation of JAK tyrosine kinase & STATs
- WSXWS motif appears to be necessary for proper protein folding & thus efficient intracellular transport & cell-surface receptor binding
- box 1 motif is required for JAK interaction &/or activation
- belongs to the type I cytokine receptor family, type 2 subfamily
- contains 4 fibronectin F3 modules
- contains 1 Ig-like (immunoglobulin-like) domain
Compartment
- cell membrane
- isoform E: secreted (probable)
Alternative splicing
named isoforms=5; A-E
Expression
- isoform A is expressed in fetal liver & in hematopoietic tissues & choroid plexus
- in adults highest expression in heart, liver, small intestine, prostate & ovary
- low level in lung & kidney
- isoform B is highly expressed in hypothalamus
- arcuate nucleus of hypothalamus[2]
- POMC & neuropeptide Y neurons
Pathology
- ob (leptin) receptor gene mutation associated with autosomal recessive obesity
Notes
- leptin increases frequency of action potentials in POMC neurons by
- depolarization through nonspecific cation channel
- reduced inhibition by neuropeptide-Y/GABA neurons[2]
More general terms
Additional terms
- leptin receptor gene-related protein; leptin receptor overlapping transcript protein; OB-R gene-related protein; OB-RGRP (LEPROT, LEPR, OBR)
- leptin receptor overlapping transcript-like 1; brain my047 protein (LEPROTL1)
- leptin; obesity factor; obese protein (LEP, OB, OBS)
References
- ↑ Tartaglia LA et al. Identification and expression cloning of a leptin receptor, OB-R. Cell 83:1263-71 1995 PMID: https://www.ncbi.nlm.nih.gov/pubmed/8548812
- ↑ 2.0 2.1 2.2 Cowley MA et al. Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 411:480-4, 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11373681
- ↑ UniProt http://www.uniprot.org/uniprot/P48357.html