Journal: Mucosal immunology
Article Title: Leptin Signaling in Intestinal Epithelium Mediates Resistance to Enteric Infection by Entamoeba histolytica
doi: 10.1038/mi.2010.76
Figure Lengend Snippet: Leptin binding to the long form LRb results in the activation and tyrosine phosphorylation of Janus kinase 2 (JAK2), which induces subsequent phosphorylation of downstream tyrosine residues (Tyr985, Tyr1077 and Tyr1138) in the intracellular tail of LRb. Phosphorylated Tyr1138 binds and mediates the phosphorylation-dependent activation of signal transducer and activator of transcription 3 (STAT3), which activates transcription of suppressor of cytokine signaling 3 (SOCS3) and other positive effectors of leptin action. Phosphorylated Tyr985 recruits the SH2-containing tyrosine phosphatase SHP-2, which activates the signaling pathway that culminates in extracellular signal-regulated kinase (ERK) activation. During prolonged stimulation, phosphorylated Tyr985 binds SOCS3 to mediate feedback inhibition of LRb signaling. Phosphorylated Tyr1077 recruits STAT5 to induce STAT5-dependent transcription activation; however, its functional effect is less clear. Signals mediated via phosphorylated Jak2 include insulin receptor substrate protein (IRS) and the PI3K/Akt pathway. The PI3K/Akt signaling is important for the LRb-mediated anti-apoptotic and pro-proliferative effects via down-regulating pro-apoptotic (eg. Bad, Bim, Bax and p53) while up-regulating anti-apoptotic/survival factors (eg. Bcl-2, Bcl-XL and Cyclin D). *Figure adapted from Febbraio MA, J Clin Invest . 2007; 117(4): 841–849.
Article Snippet: Six-week-old male C57BL/6J wild-type (B6 WT), leptin-deficient (B6.V-Lep ob /J, ob/ob) and functional leptin receptor-deficient (B6.Cg-m Lepr db /J, db/db) mice were purchased from Jackson Laboratories (Bar Harbor, ME).
Techniques: Binding Assay, Activation Assay, Phospho-proteomics, Inhibition, Functional Assay
