Figure 3. Mechanisms of JAK/STAT activation through OB-Rb.

Upon leptin (L) binding, a conformational change takes place (A) that allows juxtaposition of JAKs, which then become activated and are able to tyrosine-phosphorylate other JAKs and tyrosine residues on the receptor (B). Activation of JAK2 occurs by transphosphorylation and subsequent phosphorylation of tyrosine residues in the cytoplasmic region of the receptor. Phosphorylation of Tyr¹¹³⁸ allows association of STATs, which then become substrates of receptor-associated JAKs. Phosphorylation of STATs leads to their dissociation from the receptor and the formation of active dimers (C), which translocate to the nucleus to regulate gene expression, binding to the promoter regions of target genes (D).