Proposed signal transduction pathways in NG following receptor activation with leptin and CCK-8

Proposed signal transduction pathways in NG following receptor activation with leptin and CCK-8. There are two potential pathways for phosphorylation of STAT3. Leptin activates JAK2 phosphorylation at tyrosine 1138, which directly phosphorylates STAT3, or leptin activates PI3K via the insulin receptor substrate, leading to STAT3 phosphorylation. CCK-8 activates PI3K via Src and RhoA, which leads to phosphorylation of STAT3, suggesting that PI3K is central to the synergistic leptin/CCK STAT3 phosphorylation. The MAPK inhibitor PD98059 had no effect on leptin and CCK-8 synergism, suggesting that the leptin/CCK-8-stimulated MAPK/ERK1/2 pathway was not involved in STAT3 phosphorylation. STAT3 usually acts by stimulating the transcription of target genes, but the rapid electrophysiological effects suggest STAT3 may be involved in modifying the activity of K+ channels.

Publication

Synergistic Interaction between Leptin and Cholecystokinin in the Rat Nodose Ganglia Is Mediated by PI3K and STAT3 Signaling Pathways. (2011) Andrea Heldsinger, et al. J Biol Chem. 2011 Apr 1;286(13):11707-11715. Figure: F9. Homo sapiens

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