Dual inhibition of ErbB1 and ErbB2 in cancer by recombinant human prolidase mutant hPEPD-G278D.

ABSTRACT: ErbB1 and ErbB2 are oncogenic cell surface receptor tyrosine kinases, linked to many forms of human cancer, and are major cancer therapeutic targets. Many lines of evidence indicate that targeting ErbB1 and ErbB2 is an important cancer therapeutic approach. We recently found that a recombinant enzymatically-inactive mutant of human prolidase, i.e., hPEPD-G278D, is an inhibitory ligand of ErbB2 and strongly inhibits ErbB2-overexpressing cells in vitro and in vivo. hPEPD-G278D also binds to ErbB1. Here, we show that hPEPD-G278D binds to ErbB1 with high affinity, initially activating ErbB1 but later silencing it, and that deletion of subdomain 2 in ErbB1 extracellular domain abolishes the binding. The proliferation of ErbB1-overexpressing cells is strongly inhibited by hPEPD-G278D, regardless

SUBMITTER: Yang L 

PROVIDER: S-EPMC5173139 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature