受体酪氨酸激酶
生物
G蛋白偶联受体
G蛋白偶联受体激酶
ROR1型
计算生物学
酪氨酸激酶
受体
信号转导
受体蛋白酪氨酸激酶
细胞生物学
生物信息学
血小板源性生长因子受体
生物化学
生长因子
作者
Caitrin Crudden,Takashi Shibano,Dawei Song,Naida Suleymanova,Leonard Girnita
标识
DOI:10.1016/bs.ircmb.2018.02.006
摘要
Receptor tyrosine kinases (RTKs) such as the insulin-like growth factor type 1 receptor (IGF-1R) control important biological activities as well as being involved in pathological processes. Due to their supportive nature in many human cancers they have long been considered attractive therapeutic targets. However, lessons learnt from early targeting trials highlight that a simple “active versus inactive” state model with classical kinase-only signaling is overly simplistic and does not describe reality. A vast amount of evidence exists disproving this model and hence provides a rational explanation for failure of many targeting agents designed under such a paradigm. In addition, substantial evidence exists that the IGF-1R and other RTKs make direct use of the G protein-coupled receptor (GPCR) components G proteins, GRKs, and β-arrestins, outside of their traditional receptor family frame. In this chapter we review the evidence that RTKs can undertake a wide range of active conformations, capable of distinct downstream signal cascades and propose an RTK/GPCR functional hybrid model, while discussing the implications of such an update on therapeutic drug development pipelines.
科研通智能强力驱动
Strongly Powered by AbleSci AI