激活素信号通路拮抗剂：作用机制及潜在生物学应用

Antagonists of activin signaling: mechanisms and potential biological applications.

作者信息

Harrison Craig A, Gray Peter C, Vale Wylie W, Robertson David M

机构信息

Prince Henry's Institute of Medical Research, 246 Clayton Road, Clayton, VIC 3168, Australia.

出版信息

Trends Endocrinol Metab. 2005 Mar;16(2):73-8. doi: 10.1016/j.tem.2005.01.003.

DOI:10.1016/j.tem.2005.01.003

PMID:15734148

Abstract

Activins are members of the transforming growth factor-beta (TGF-beta) superfamily that control many physiological processes such as cell proliferation and differentiation, immune responses, wound repair and various endocrine activities. Activins elicit these diverse biological responses by signaling via type I and type II receptor serine kinases. Recent studies have revealed details of the roles of inhibin, betaglycan, follistatin and its related protein follistatin-related gene (FLRG), Cripto and BAMBI in antagonizing activin action, and exogenous antagonists against the activin type I (SB-431542 and SB-505124) and type II (activin-M108A) receptors have been developed. Understanding how activin signaling is controlled extracellularly is the first step in providing treatment for wound healing and for disorders such as cachexia and cancer, which result from a deregulated activin pathway.

摘要

激活素是转化生长因子-β（TGF-β）超家族的成员，可控制许多生理过程，如细胞增殖与分化、免疫反应、伤口修复及各种内分泌活动。激活素通过I型和II型受体丝氨酸激酶发出信号，引发这些多样的生物学反应。最近的研究揭示了抑制素、β聚糖、卵泡抑素及其相关蛋白卵泡抑素相关基因（FLRG）、Cripto和BAMBI在拮抗激活素作用中的作用细节，并且已经开发出针对激活素I型（SB-431542和SB-505124）和II型（激活素-M108A）受体的外源性拮抗剂。了解激活素信号在细胞外是如何被控制的，是为伤口愈合以及恶病质和癌症等由激活素途径失调导致的疾病提供治疗的第一步。