Glucose-mediated N-glycosylation of RPTPα affects its subcellular localization and Src activation

Receptor-type protein tyrosine phosphatase alpha (RPTP alpha) 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 RPTP alpha 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 RPTP alpha from Golgi apparatus to plasma membrane, enhance the interaction of RPTP alpha with Src, which in turn enhances the activation of Src and ultimately promotes tumor development. Our results identified the N-glycosylation modifications of RPTP alpha, and linked it to glucose starvation and Src activation for promoting tumor development, which provides new evidence for the potential antitumor therapy.