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. 2022 Dec 6;23(23):15440. doi: 10.3390/ijms232315440

Figure 6.

Figure 6

Schematic diagram of phosphoPROTACs. PhosphoPROTAC consists of an RTK phosphorylation sequence, VHL binding sequence and a poly-D-Arginine sequence connected by a linker. When the RTK is activated, the tyrosine of the RTK phosphorylation sequence is phosphorylated, recruits and activates POI with PTB and SH2 domains. The peptidic VHL binding sequence following hydroxylation of the proline residue recruits the VHL E3 ligase to mediate polyubiquitination and degradation of the POI, thereby inactivating tyrosine kinase signaling. RTK: receptor tyrosine kinase; VHL: von Hippel-Lindau.