Transforming growth factor-β receptors:versatile mechanisms of ligand activation  

作　　者：Zheng-Jie Chia Ying-nan Cao Peter J.Little Danielle Kamato 

机构地区：[1]School of Pharmacy,The University of Queensland,Brisbane,QLD,4102,Australia [2]Discovery Biology,School of Environment and Science,Griffith University,Brisbane,QLD,4111,Australia [3]Griffith Institute for Drug Discovery,Griffith University,Brisbane,QLD,4111,Australia [4]Department of Pharmacy,Guangzhou Xinhua University,Guangzhou,510520,China

出　　处：《Acta Pharmacologica Sinica》2024年第7期1337-1348,共12页中国药理学报（英文版）

基　　金：supported by a Future Leader Fellowship (106605)from the National Heart Foundation of Australia.

摘　　要：Transforming growth factor-β(TGF-β)signaling is initiated by activation of transmembrane TGF-βreceptors(TGFBR),which deploys Smad2/3 transcription factors to control cellular responses.Failure or dysregulation in the TGF-βsignaling pathways leads to pathological conditions.TGF-βsignaling is regulated at different levels along the pathways and begins with the liberation of TGF-βligand from its latent form.The mechanisms of TGFBR activation display selectivity to cell types,agonists,and TGF-βisoforms,enabling precise control of TGF-βsignals.In addition,the cell surface compartments used to release active TGF-βare surprisingly vibrant,using thrombospondins,integrins,matrix metalloproteinases and reactive oxygen species.The scope of TGFBR activation is further unfolded with the discovery of TGFBR activation initiated by other signaling pathways.The unique combination of mechanisms works in series to trigger TGFBR activation,which can be explored as therapeutic targets.This comprehensive review provides valuable insights into the diverse mechanisms underpinning TGFBR activation,shedding light on potential avenues for therapeutic exploration.

关 键 词：TGFBR receptor Smads THROMBOSPONDINS matrix metalloproteinases INTEGRINS TRANSACTIVATION 

分 类 号：R96[医药卫生—药理学]