Fyn mediates leptin actions in the thymus of rodents.
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.


RESULTS
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 addition, the inhibition of Fyn significantly modifies the effects of leptin on thymic cytokine expression.


CONCLUSIONS
Therefore, in the thymus, Fyn acts as a tyrosine kinase that transduces the leptin signal independently of JAK2 activation, and mediates some of the immunomodulatory effects of leptin in this tissue.
Girasol
Alessandra
A
Department of Internal Medicine, University of Campinas, Campinas, Brazil.
Albuquerque
Gabriela G
GG
Mansour
Eli
E
Araújo
Eliana P
EP
Degasperi
Giovanna
G
Denis
Raphael G
RG
Carvalheira
José B
JB
Saad
Mário J
MJ
Velloso
Lício A
LA
D000818:Animals; D002469:Cell Separation; D005786:Gene Expression Regulation; D020738:Leptin / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D054411:Receptors, Leptin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013950:Thymus Gland / Q000166:cytology*
D020738:Leptin; D054411:Receptors, Leptin; D019869:Phosphatidylinositol 3-Kinases; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn