Receptor for obesity factor (leptin). On ligand binding, mediates signaling through JAK2/STAT3. Involved in the regulation of fat metabolism and, in a hematopoietic pathway, required for normal lymphopoiesis. May play a role in reproduction. Can also mediate the ERK/FOS signaling pathway.
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.
Belongs to the type I cytokine receptor family. Type 2 subfamily. Contains 4 fibronectin type-III domains. Contains 1 Ig-like (immunoglobulin-like) domain.
The cytoplasmic domain may be essential for intracellular signal transduction by activation of JAK tyrosine kinase and STATs. The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding. The box 1 motif is required for JAK interaction and/or activation.
On ligand binding, phosphorylated on two conserved C-terminal tyrosine residues (isoform B only) by JAK2. Tyr-986 is required for complete binding and activation of PTPN11, ERK/FOS activation and, for interaction with SOCS3 (By similarity). Phosphorylation on Tyr-1141 is required for STAT3 binding/activation.