生长激素受体介导的信号转导机制研究进展

›› 2014, Vol. 41 ›› Issue (12): 186-189.

生长激素受体介导的信号转导机制研究进展

吴天成, 兰海楠, 马思慧, 杨欢, 李雨萌, 洪盼, 李雁强, 刘海艳, 张晓音, 郑鑫

吉林农业大学动物科学技术学院, 吉林长春 130118

收稿日期:2014-05-05 出版日期:2014-12-20 发布日期:2014-12-25
通讯作者: 郑鑫
作者简介:吴天成(1988－),男,吉林人,硕士生,研究方向:动物遗传育种与繁殖.
基金资助:
国家科技支撑计划课题(2013BAD10B03).

Research Progress on Signal Transduction Mechanisms Underlying Growth Hormone Receptor Action

WU Tian-cheng, LAN Hai-nan, MA Si-hui, YANG Huan, LI Yu-meng, HONG Pan, LI Yan-qiang, LIU Hai-yan, ZHANG Xiao-yin, ZHENG Xin

College of Animal Science & Technology, Jilin Agricultural University, Changchun 130118, China

Received:2014-05-05 Online:2014-12-20 Published:2014-12-25

摘要/Abstract

摘要： 生长激素(growth hormone,GH)对动物的生长发育具有重要的生理作用.GH与生长激素受体(growth hormone receptor,GHR)结合后才会发挥一系列的生理作用.近年来,人们对GHR结构和功能的研究取得了巨大的进展,并取得了一些重大的突破.现在已清楚了GH-GHR轴激活一些相关的信号转导通路,但并非所有的通路都依赖酪氨酸激酶.作者从以下几个方面总结了GHR作用下的信号转导机制的研究进展:GHR的结构与功能;依赖JAK2的相关信号通路;不依赖JAK2的相关信号通路;GHR信号负调控因子.阐明这些复杂机制,对进一步了解GH对动物不同的生理和病理作用具有重要意义.

关键词: 生长激素受体; JAK2; Src激酶; 细胞信号抑制因子

Abstract: Growth hormone (GH) has important physiological roles on animals in growth and development. GH plays a series of physiological effects after binding to growth hormone receptor (GHR). Our understanding of the mechanisms of action of GH and its receptor, the GHR, has advanced significantly in the last decade and has provided some important surprises. It is now clear that the GH-GHR axis activates a number of inter-related signalling pathways, not all of which are dependent on the intracellular tyrosine kinase, JAK2 as originally postulated. This paper summarizes the following aspects of signal transduction mechanisms progress under the GHR role:GHR structure and function;GHR signalling including JAK2-dependent signalling and JAK2-independent signalling; negative regulators of GHR signalling. Continued emphasis on elucidation of these complex mechanisms is critical to provide further insights into the animal diverse physiological and pathophysiological effects of GH.

Key words: growth hormone receptor; JAK2; Src kinases; suppressors of cytokine signalling

中图分类号:

Q507

吴天成, 兰海楠, 马思慧, 杨欢, 李雨萌, 洪盼, 李雁强, 刘海艳, 张晓音, 郑鑫. 生长激素受体介导的信号转导机制研究进展[J]. , 2014, 41(12): 186-189.

WU Tian-cheng, LAN Hai-nan, MA Si-hui, YANG Huan, LI Yu-meng, HONG Pan, LI Yan-qiang, LIU Hai-yan, ZHANG Xiao-yin, ZHENG Xin. Research Progress on Signal Transduction Mechanisms Underlying Growth Hormone Receptor Action[J]. , 2014, 41(12): 186-189.

参考文献

1 李维. 猪生长激素模拟肽作用机制的研究[D]. 长春:吉林农业大学,2013.
2 杨艳红, 付志玲,兰海楠,等. 生长激素激活受体机理的研究进展[J]. 中国畜牧兽医,2013,40(10):148～151.
3 姒健敏,高敏,曹倩,等. 生长激素及其受体在萎缩性胃炎中的表达及临床意义探讨[J]. 中国消化杂志,2012,8(22):499.
4 Alves dos Santos C M, ten Broeke T, Strous G J. Growth hormone receptor ubiquitination, endocytosis and degradation are independent of signal transduction via Janus kinase 2[J]. Biol Chem,2001,276(35):32635～32641.
5 Barclay J L, Kerr L M, Arthur L, et al. In vivo targeting of the growth hormone receptor (GHR) Box1 sequence demonstrates that the GHR does not signal exclusively through JAK2[J]. Mol Endocrinol, 2010,24(1):204～217.
6 Bernabeu I, Alvarez-Escolá C, Quinteiro C, et al. The exon 3-deleted growth hormone receptor is associated with better response to pegvisomant therapy in acromegaly[J]. Clin Endocrinol Metab, 2010,95(1):222～229.
7 de Vos A M, Ultsch M, Kossiakoff A A. Human growth hormone and extracellular domain of its receptor:Crystal structure of the complex[J]. Science, 1992, 255(5042):306～312.
8 Deng L, He K, Wang X, et al. Determinants of growth hormone receptor down regulation[J]. Mol Endocrinol, 2007, 21(7):1537～1551.
9 Flores-Morales A, Greenhalgh C J, Norstedt G, et al. Negative regulation of growth hormone receptor signalling[J]. Mol Endocrinol, 2006, 20(2):241～253.
10 Frank S J, Fuchs S Y. Modulation of growth hormone receptor abundance and function:Roles for the ubiquitin proteasome system[J]. Biochim Biophys Acta, 2008, 1782:785～794.
11 Gent J, Van Kerhof P, Roza M, et al. Ligand-independent growth hormone receptor dimerization occurs in the endoplasmic reticulum and is required for ubiquitin system-dependent endocytosis[J]. Proc Natl Acad Sci USA, 2002, 99:9858～9863.
12 Hansen J A, Lindberg K, Hilton D J, et al. Mechanism of inhibition of growth hormone receptor signalling by suppressor of cytokine signalling proteins[J]. Mol Endocrinol, 1999, 13:1832～1843.
13 Higham C E, Trainer P J. Growth hormone excess and the development of growth hormone receptor antagonists[J]. Exp Physiol, 2010, 93(11):1157～1169.
14 Leung D W, Spencer S A, Cachianes G, et al. Growth hormone receptor and serum binding protein:Purification, cloning and expression[J]. Nature, 1987, 330(6148):537～543.
15 Litterst C M,Kliem S, Lodrini M,et al. Coactivators in gene regulation by STAT5[J]. Vitam Horm,2005,70:359～386.
16 Ram P A, Waxman D J. SOCS/CIS protein inhibition of growth hormone-stimulated STAT5 signaling by multiple mechanisms[J]. Biol Chem, 1999, 274:35553～35561.
17 Rosenfeld R G, Kofoed E, Buckway C, et al. Identification of the first patient with a conformed mutation of the JAK-STAT system[J]. Pediatr Nephrol, 2005, 20(3):303～305.
18 Rowlinson S W, Yoshizato H, Barclay J L, et al. An agonist-induced conformational change in the growth hormone receptor determines the choice of signalling pathway[J]. Nat Cell Biol, 2008, 10(6):740～747.
19 Starr R, Metcalf D, Elefanty A G, et al. Liver degeneration and lymphoid deficiencies in mice lacking suppressor of cytokine signaling-1[J]. Proc Natl Acad Sci USA, 1998, 95(24):14395～14399.
20 Tsushima T, Friesen H G. Radio receptor assay for human growth hormone[J]. J Clin Endocrinol Metab, 1973, 37(2):334～337.
21 Waters M J, Books A J. Growth hormonal receptor:Structure function relationships[J]. Horm Res Pediatr,2011, 76(Suppl 1):12～16.
22 Wei Y, Rhani Z, Goodyer C G. Characterization of growth hormone receptor messenger ribonucleic acid variants in human adipocytes[J]. Clin Endocrinol Metab, 2006, 91(5):1901～1908.
23 Yang N, Langenheim J F, Wang X, et al. Activation of growth hormone receptors by growth hormone and growth hormone ant agonist dimers:Insights into receptor triggering[J].Mol Endocrinal, 2008, 22(4):978～988.

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