Leptin Receptor ELISA Kit, Human

Leptin binding to the extracellular domain of the LRb dimer activates the Jak2 tyrosine kinase that associates with OBRl via the Box 1 motif and intracellular amino acids 31–36 of LRb. Activated Jak2 tyrosine phosphorylates itself and Tyr985 and Tyr1138 on the intracellular tail of OBRl. Phosphorylated Tyr1138 binds and mediates the phosphorylation-dependent activation of signal transducer and activator of transcription 3 (STAT3), which activates transcription of suppressor of cytokine signaling 3 (SOCS3) (a feedback inhibitor of OBRl signaling) and pro-opiomelanocortin (POMC) (an anorexigenic neuropeptide) and inhibits the transcription of agouti-related protein (AgRP) (an orexigenic neuropeptide). Phosphorylated Tyr985 recruits the SH2-containing tyrosine phosphatase SHP-2, which is itself phosphorylated and binds growth factor receptor binding 2 (Grb-2) to activate the signaling pathway that culminates in extracellular signal-regulated kinase (ERK) activation. During prolonged stimulation, after induction of SOCS3 protein, phosphorylated Tyr985 also mediates binding of SOCS3. Signals mediated via unidentified tyrosine phosphorylation sites on OBRl include the tyrosine phosphorylation of insulin receptor substrate (IRS) proteins and a minor component of ERK activation.² It has been shown that that both OBRs and OBRl had the ability to activate JAK2 and IRS-1 tyrosine phosphorylation in a leptin-dependent manner in transiently transfected cell lines. Both isoforms were also able to induce leptin-dependent activation of MAPK in both transiently transfected cells and in stable CHO cell lines. It is clear that OBRl more robustly activate these pathways than does OBRs. In contrast, only the long form of the leptin receptor had the ability to activate STAT3 tyrosine phosphorylation and to stimulated c-fos gene transcription.³