fyn mediates leptin actions in the thymus of rodents菲英岛瘦素介导的行动在啮齿动物的胸腺.pdfVIP

Fyn Mediates Leptin Actions in the Thymus of Rodents 1 1 1 ´ 2 1 Alessandra Girasol , Gabriela G. Albuquerque , Eli Mansour , Eliana P. Araujo , Giovanna Degasperi , 1 ´ 1 ´ 1 ´ 1 Raphael G. Denis , Jose B. Carvalheira , Mario J. Saad , Lıcio A. Velloso * 1 Department of Internal Medicine, University of Campinas, Campinas, Brazil, 2 Department of Nursing, University of Campinas, Campinas, Brazil Abstract Background: Several effects of leptin in the immune system rely on its capacity to modulate cytokine expression and apoptosis in the thymus. Surprisingly, some of these effects are dependent on signal transduction through the IRS1/PI3- kinase, but not on the activation of JAK2. Since all the well known effects of leptin in different cell types and tissues seem to be dependent on JAK2 activation, we hypothesized that, at least for the control of thymic function, another, unknown kinase could mediate the transduction of the leptin signal from the ObR towards the IRS1/PI3-kinase signaling cascade. Methodology/Principal Findings: Here, by employing immunoblot, real-time PCR and flow citometry we show that the tyrosine kinase, Fyn, is constitutively associated with the ObR in thymic cells. Following a leptin stimulus, Fyn undergoes an activating tyrosine phosphorylation and a transient association with IRS1. All these effects are independent of JAK2 activation and, upon Fyn inhibition, the signal transduction towards IRS1/PI3-kinase is abolished. In ad