Figure 1.

Leptin receptor subtypes. Six different isoforms of ObR have been identified, denoted as ObRa, ObRb, ObRc, ObRd, ObRe, and ObRf. Each receptor subtype shares two cytokine-binding homology regions (CHR1 and CHR2) with CHR2 representing the main binding site for leptin, an IgG-like domain, and two fibronectin type 3 domains (FN3) within its C-terminal. All isoforms have transmembrane regions except the ObRe receptor, which functions as a soluble leptin binding receptor not anchored to the cell membrane and which binds circulating leptin, thereby regulating leptin bioavailability and functionality but is unable to transduce any downstream signalling. The intracellular N-terminal domain expresses a BOX-1 motif, which is critical for JAK-2 binding. The OBRb receptor is the only long isoform to also express a BOX-2 motif, which facilitates the activation of the JAK2/STAT transduction pathway. Moreover, ObRb contains 3 tyrosine residues (Tyr986, Tyr1076, and Tyr1141) whose phosphorylation enables STAT3/STAT5 activation. The short isoforms ObRa,c,d,f have only one intracellular domain (Box 1) and therefore limited signalling capacity. Created with PowerPoint software (Microsoft Office 365).