基瘦蛋白与其受体介导的信号转导  

Signal transduction mediated by leptin and its receptor

作　　者：司艺玲[1] 颜光涛[1] 

机构地区：[1]解放军总医院基础医学所生物化学研究室,北京100853

出　　处：《生命的化学》2008年第5期574-578,共5页Chemistry of Life

摘　　要：瘦蛋白是由肥胖基因编码的一种16kDa的活性蛋白质,其三维结构与长链细胞因子家族相似。瘦蛋白受体属I类细胞因子受体家族,包括6种剪接体(OB-Ra、b、c、d、e、f),广泛分布于中枢及外周组织,其中的功能性受体(OB-Rb)与瘦蛋白结合后可激活Janus激酶/信号转导及转录激活蛋白(JAK-STAT)途径、原活化的蛋白激酶(MAPK)途径、磷脂酰肌醇-3-激酶(PI3K)/磷酸二酯酶3B(PDE3B)/cAMP途径、5'-AMP活化的蛋白激酶(AMPK)等主要信号途径,在调节能量代谢、神经内分泌和免疫反应等方面发挥多效能作用,并参与肥胖、糖尿病、自身免疫性疾病等的发生发展过程。该文主要结合瘦蛋白及其受体的结构和功能对二者相互作用的模式和信号通路作一综述。Leptin is a versatile 16-kDa peptide product of OB gene, with a tertiary structure similar to those of members of the long-chain helical cytokine family. Leptin receptor （OB-R）, which shows structural similarity to the class I cytokine receptor family and ubiquitously distributes in almost all tissues, is produced in several alternatively splice isoforms, designated OB-Ra, b, c, d, e and f. The full length isoform （OB-Rb）, which contains intracellular motifs, is considered to be the functional receptor. The binding and interaction between Leptin and OB-Rb are required for the activation of several signaling pathways, including JAK-STAT （Janus kinases-signal transducers and activators of transcription） cascade, MAPK （mitogen-activated protein kinase） cascade, PI3K （phosphoinositide 3-kinase）/PDE3B （phosphodiesterase 3B）/cAMP pathway, AMPK （5＇-AMP-activated protein kinase） pathway. Then, leptin can operate to modulate complex functions including energy metabolism, neuroendocrine, immunity, and also participate in some pathophysiological processes, such as obesity, diabetes, autoimmune diseases. Here, we discuss the structure and function of leptin and its receptor, as well as the mechanisms of their interaction and relevant signaling pathway.

关 键 词：瘦蛋白 受体 信号转导 细胞因子 

分 类 号：Q51[生物学—生物化学]