RESUMO
The adipocyte-secreted hormone leptin participates in the regulation of hematopoiesis and enhances proliferation of hematopoietic cells. We used an adaptation of the MAPPIT mammalian two-hybrid method to study leptin signalling in a hematopoietic setting. We confirmed the known interactions of suppressor of cytokine signalling 3 (SOCS3) and STAT5 with the Y985 and Y1077 motifs of the leptin receptor, respectively. We also provide evidence for novel interactions at the Y1077 motif, including phospholipase C gamma and several members of the SOCS protein family, further underscoring the important role of the Y1077 motif in leptin signalling.
Assuntos
Células-Tronco Hematopoéticas/metabolismo , Receptores de Superfície Celular/metabolismo , Fator de Transcrição STAT5/metabolismo , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Técnicas do Sistema de Duplo-Híbrido , Motivos de Aminoácidos , Animais , Células Cultivadas , Humanos , Leptina/metabolismo , Camundongos , Ratos , Receptores para Leptina , Fator de Transcrição STAT5/genética , Transdução de Sinais , Proteínas Supressoras da Sinalização de Citocina/genéticaRESUMO
Leptin was originally discovered as an adipocyte-derived hormone involved in the central control of body weight and energy homeostasis. It is now clear that leptin is a pleiotropic cytokine, with activities on many peripheral cell types. These findings may help explain the surprising role of leptin in pathophysiological processes. Recent evidence suggests that leptin contributes to atherosclerosis and to the increased risk of cardiovascular disease in obese people. Leptin also appears to be involved in T-cell-dependent immunity and possibly in the development and maintenance of certain autoimmune diseases. Here, we review the role of leptin in cardiovascular and autoimmune diseases, and also briefly address the potential therapeutic use of leptin antagonists.