Data from: RNA sequencing to determine the contribution of kinase receptor transactivation to G protein coupled receptor signalling in vascular smooth muscle cells

Link at the Gene Expression Omnibus provides related data for linked article.

G protein coupled receptor (GPCR) signalling covers three major mechanisms. GPCR agonist engagement allows for the G proteins to bind to the receptor leading to a classical downstream signalling cascade. The second mechanism is via the utilization of the β-arrestin signalling molecule and thirdly via transactivation dependent signalling. GPCRs can transactivate protein tyrosine kinase receptors (PTKR) to activate respective downstream signalling intermediates. In the past decade GPCR transactivation dependent signalling was expanded to show transactivation of serine/threonine kinase receptors (S/TKR). Kinase receptor transactivation enormously broadens the GPCR signalling paradigm. This work utilizes next generation RNA-sequencing to study the contribution of transactivation dependent signalling to total protease activated receptor (PAR)-1 signalling. Transactivation, assessed as gene expression, accounted for 50 percent of the total genes regulated by thrombin acting through PAR-1 in human coronary artery smooth muscle cells. GPCR transactivation of PTKRs is approximately equally important as the transactivation of the S/TKR with 209 and 177 genes regulated respectively, via either signalling pathway. This work shows that genome wide studies can provide powerful insights into GPCR mediated signalling pathways.

基因表达综合数据库（Gene Expression Omnibus）中的链接可获取与该关联文章相关的实验数据。

G蛋白偶联受体（G protein coupled receptor, GPCR）信号转导涵盖三大核心机制：GPCR激动剂与受体结合后，可促使G蛋白与受体结合，进而启动经典的下游信号级联反应；其二为利用β抑制蛋白（β-arrestin）信号分子介导的通路；其三则是反式激活依赖型信号转导。
既往研究证实，GPCR可反式激活蛋白酪氨酸激酶受体（protein tyrosine kinase receptors, PTKR），以激活对应的下游信号中间产物。近十年来，GPCR反式激活依赖型信号转导的研究范畴进一步拓展，现已发现其可反式激活丝氨酸/苏氨酸激酶受体（serine/threonine kinase receptors, S/TKR）。激酶受体的反式激活极大地拓宽了GPCR信号转导的研究范式。
本研究采用下一代RNA测序（RNA-sequencing）技术，探究反式激活依赖型信号转导在总蛋白酶激活受体（protease activated receptor, PAR）-1信号转导中的占比。在人冠状动脉平滑肌细胞中，以基因表达水平评估的反式激活事件，占凝血酶通过PAR-1调控的全部基因的50%。GPCR对PTKRs的反式激活与对S/TKRs的反式激活重要性大致相当，二者分别通过各自信号通路调控209和177个基因。
本研究表明，全基因组层面的研究可为GPCR介导的信号转导通路研究提供极具价值的深入见解。