受体型酪氨酸磷酸酶α(RPTPα)是典型的PTPs之一，它在与癌症相关的许多细胞过程中发挥着不可或缺的作用。它被认为是Src激活的最强调控癌基因，但其生物学功能如何受到翻译后修饰的调节仍不清楚。在这里，我们展示了RPTPα的细胞外段在N21、N36、N68、N80、N86、N104和N124位点处高度N-糖基化。这种由葡萄糖浓度介导的N-糖基化修饰改变了RPTPα的亚细胞定位，从高尔基体到质膜，增强了RPTPα与Src的相互作用，从而增强了Src的激活，并最终促进了肿瘤的发展。我们的结果确定了RPTPα的N-糖基化修饰，并将其与葡萄糖饥饿和Src激活联系起来，以促进肿瘤的发展，为潜在的抗肿瘤疗法提供了新的证据。©2023年。作者(们)独家许可Springer Nature Limited。

Receptor-type protein tyrosine phosphatase α (RPTPα) is one of the typical PTPs that play indispensable roles in many cellular processes associated with cancers. It has been considered as the most powerful regulatory oncogene for Src activation, however it is unclear how its biological function is regulated by post-translational modifications. Here, we show that the extracellular segment of RPTPα is highly N-glycosylated precisely at N21, N36, N68, N80, N86, N104 and N124 sites. Such N-glycosylation modifications mediated by glucose concentration alter the subcellular localization of RPTPα from Golgi apparatus to plasma membrane, enhance the interaction of RPTPα with Src, which in turn enhances the activation of Src and ultimately promotes tumor development. Our results identified the N-glycosylation modifications of RPTPα, and linked it to glucose starvation and Src activation for promoting tumor development, which provides new evidence for the potential antitumor therapy.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.