Phosphorylation of Tyr985 activates signaling related with SH2-containing protein tyrosine phosphatase 2 (SHP2) and mediates the leptin-stimulated activation of the extracellular signal-related kinase (ERK) pathway, which executes the important functions in thermogenesis and anti-obesity of leptin [35, 36]. Here, LEP is linked to obesity due to melanocortin 4 receptor deficiency.