Recent advances in growth hormone signaling
Recent advances in growth hormone signaling
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DOI：
10.1007/s11154-007-9025-5
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发表时间：
2006-12-01
影响因子：
8.2
通讯作者：
Carter-Su, Christin
中科院分区：
文献类型：
--
作者：
Lanning, Nathan J.;Carter-Su, Christin
生长激素（GH）是整体身体生长的主要调节因素，如循环GH水平异常或GH受体（GHR）中断的人的身高极限所证明的。生长激素还影响新陈代谢，心脏和免疫功能，精神敏捷性和衰老。目前，GH被用于治疗各种临床疾病，包括促进矮小儿童的生长，治疗GH缺乏症和HIV相关性消瘦的成人。为了帮助揭示以前未认识到的功能的生长激素，更好地了解已知的功能生长激素，并避免不良后果，往往与外源性生长激素管理，仔细描绘的分子机制，生长激素诱导其不同的影响是必要的。GH是一种肽类激素，由垂体前叶分泌到循环中，作用于表达GHR的各种靶组织。GH与GHR的结合激活酪氨酸激酶Janus激酶2（JAK 2），从而启动多种信号传导级联，导致多种生物学反应，包括细胞增殖、分化和迁移、细胞凋亡预防、细胞骨架重组和代谢途径调节。已经鉴定了许多由GH激活的信号蛋白和途径，包括JAK、信号转导子和转录激活子（Stats）、促分裂原活化蛋白激酶（MAPK）途径和磷脂酰肌醇3 '-激酶（PI 3 K）途径。虽然这些信号转导途径已得到很好的表征，但GH激活这些途径的方式、这些途径诱导的下游信号以及与其他途径的串扰尚未完全了解。最近的研究结果为我们理解GH诱导的这些下游信号和终止GH信号传导的机制提供了重要信息，并确定了新的GH信号传导蛋白和途径。本文将重点介绍其中的一些发现，其中许多是意想不到的，其中一些挑战以前持有的信念GH信号的机制。
Growth hormone (GH) is a major regulatory factor for overall body growth as evidenced by the height extremes in people with abnormal circulating GH levels or GH receptor (GHR) disruptions. GH also affects metabolism, cardiac and immune function, mental agility and aging. Currently, GH is being used therapeutically for a variety of clinical conditions including promotion of growth in short statured children, treatment of adults with GH deficiency and HIV-associated wasting. To help reveal previous unrecognized functions of GH, better understand the known functions of GH, and avoid adverse consequences that are often associated with exogenous GH administration, careful delineation of the molecular mechanisms whereby GH induces its diverse effects is needed. GH is a peptide hormone that is secreted into the circulation by the anterior pituitary and acts upon various target tissues expressing GHR. GH binding of GHR activates the tyrosine kinase Janus kinase 2 (JAK2), thus initiating a multitude of signaling cascades that result in a variety of biological responses including cellular proliferation, differentiation and migration, prevention of apoptosis, cytoskeletal reorganization and regulation of metabolic pathways. A number of signaling proteins and pathways activated by GH have been identified, including JAKs, signal transducers and activators of transcription (Stats), the mitogen activated protein kinase (MAPK) pathway, and the phosphatidylinositol 3'-kinase (PI3K) pathway. Although these signal transduction pathways have been well characterized, the manner by which GH activates these pathways, the downstream signals induced by these pathways, and the cross-talk with other pathways are not completely understood. Recent findings have added vital information to our understanding of these downstream signals induced by GH and mechanisms that terminate GH signaling, and identified new GH signaling proteins and pathways. This review will highlight some of these findings, many of which are unexpected and some of which challenge previously held beliefs about the mechanisms of GH signaling.