Fig. 3.

^ErbB2PP_PI3K, a phosphoPROTAC that conditionally targets PI3K for degradation upon ErbB2 activation. (A) Streptavidin pulldowns from MCF-7 cells using biotinylated peptides demonstrate efficacy and phospho-dependence of a selected dual phosphotyrosine-containing ErbB3 sequence to bind PI3K p85. Pulldowns electrophoresed and immunoblotted with anti-p85 antibody as described in Materials and Methods. (B) ^ErbB2PP_PI3K-mediated degradation of PI3K is target specific and blocks NRG-dependent Akt activation in MCF-7 cells. (C) Null-phosphoPROTAC ^ErbB2NP_PI3K cannot cause degradation of PI3K p85 even in the presence of neuregulin-activated ErbB2/ErbB3 signaling.