Angiogenin (ANG) is a secreted ribonuclease (RNase) with cell-type- and context-specific roles in growth, survival, and regeneration. Although these functions require receptor-mediated endocytosis and appropriate subcellular localization, the identity of the cell surface receptor remains undefined. Here, we show that plexin-B2 (PLXNB2) is the functional receptor for ANG in endothelial, cancer, neuronal, and normal hematopoietic and leukemic stem and progenitor cells. Mechanistically, PLXNB2 mediates intracellular RNA processing that contribute to cell growth, survival, and regenerative capabilities of ANG. Antibodies generated against the ANG-binding site on PLXNB2 restricts ANG activity in vitro and in vivo, resulting in inhibition of established xenograft tumors, ANG-induced neurogenesis and neuroprotection, levels of pro-self-renewal transcripts in hematopoietic and patient-derived leukemic stem and progenitor cells, and reduced progression of leukemia in vivo. PLXNB2 is therefore required for the physiological and pathological functions of ANG and has significant therapeutic potential in solid and hematopoietic cancers and neurodegenerative diseases.

中文翻译：

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Plexin-B2介导血管生成素的生理和病理功能。

血管生成素（ANG）是一种分泌型核糖核酸酶（RNase），在生长，存活和再生中具有细胞类型和环境特定的作用。尽管这些功能需要受体介导的内吞作用和适当的亚细胞定位，但是细胞表面受体的身份仍然不确定。在这里，我们显示神经丛蛋白B2（PLXNB2）是血管内皮细胞，癌症，神经元和正常造血干细胞以及白血病干细胞和祖细胞中ANG的功能性受体。从机制上讲，PLXNB2介导细胞内RNA加工，这有助于ANG的细胞生长，存活和再生能力。针对PLXNB2上ANG结合位点产生的抗体在体外和体内均会限制ANG的活性，从而抑制已建立的异种移植肿瘤，ANG诱导的神经发生和神经保护，造血干细胞和患者来源的白血病干细胞和祖细胞中自我更新转录本的水平，并降低体内白血病的进展。因此，PLXNB2对于ANG的生理和病理功能是必需的，并且在实体和造血癌以及神经退行性疾病中具有显着的治疗潜力。