Cell Logistics Research Center and School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.
Yale Cardiovascular Research Center and Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
FASEB J. 2021 Mar;35(3):e21386. doi: 10.1096/fj.202002071R.
Bone Morphogenetic Protein (BMP) signaling regulates diverse biological processes. Upon ligand binding, BMP receptors (BMPRs) phosphorylate SMAD1/5 and other noncanonical downstream effectors to induce transcription of downstream targets. However, the precise role of individual BMP receptors in this process remains largely unknown due to the complexity of downstream signaling and the innate promiscuity of ligand-receptor interaction. To delineate unique downstream effectors of individual BMPR1s, we analyzed the transcriptome of human umbilical endothelial cells (HUVECs) expressing three distinct constitutively active BMPR1s of which expression was detected in endothelial cells (ECs). From our analyses, we identified a number of novel downstream targets of BMPR1s in ECs. More importantly, we found that each BMPR1 possesses a distinctive set of downstream effectors, suggesting that each BMPR1 is likely to retain unique function in ECs. Taken together, our analyses suggest that each BMPR1 regulates downstream targets non-redundantly in ECs to create context-dependent outcomes of the BMP signaling.
骨形态发生蛋白（BMP）信号转导调节多种生物学过程。配体结合后，BMP 受体（BMPRs）磷酸化 SMAD1/5 和其他非经典下游效应物，诱导下游靶基因的转录。然而，由于下游信号的复杂性和配体-受体相互作用的固有混杂性，单个 BMP 受体在这个过程中的精确作用在很大程度上仍然未知。为了描绘单个 BMPR1 的独特下游效应物，我们分析了表达三种不同组成性激活的 BMPR1 的人脐静脉内皮细胞（HUVECs）的转录组，其中在血管内皮细胞（ECs）中检测到了表达。从我们的分析中，我们确定了 ECs 中 BMPR1 的许多新的下游靶标。更重要的是，我们发现每个 BMPR1 都具有独特的下游效应物集，这表明每个 BMPR1 可能在 ECs 中保留独特的功能。总之，我们的分析表明，每个 BMPR1 都以非冗余的方式调节 ECs 中的下游靶标，以产生 BMP 信号的上下文相关结果。
