Figure 2.

Leptin binds to the LEPR and mediates multiple downstream pathways. The JAK/STAT pathway is mediated via homo-oligomerization of JAK2, with subsequent phosphorylation and activation of STAT transcription factors, such as CPT1B and c-myc. JAK also phosphorylates Tyr985, leading to phosphorylation of SHP2 and downstream activation of ERK and associated gene expression, including the oncogene c-fos. JAK also leads to activation of the PI3K pathway, whereby AKT is phosphorylated and mTOR is subsequently activated, leading to expression of EIF4E and CAD. JNK is another pathway activated by JAK, leading to downstream expression of genes including c-Jun (oncogene) and MMP7. Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography © 2018. All Rights Reserved.