Development of a Peptide Inhibitor Targeting the C-SH2 Domain of the SHP2 Phosphatase.

ABSTRACT: Src homology 2 (SH2) domain-containing phosphatase 2 (SHP2) mediates important signal transduction upon cell surface receptor stimulation, regulating multiple cellular functions. In addition to the catalytically active phosphotyrosine (pTyr) phosphatase domain, SHP2 contains two regulatory pTyr-binding domains: the N-SH2 and C-SH2 domains. While the role of the N-SH2 domain is well understood, the role of the C-SH2 domain is less clear. To support studies on the involvement of the domains in SHP2 function, herein, the development of a peptide inhibitor containing a nonhydrolysable pTyr mimetic, which selectively binds to the C-SH2 domain of SHP2 and blocks its protein-protein interactions, is described. Incorporation of the pTyr mimetic l-O-malonyltyrosine (l-OMT) results in robust binding

SUBMITTER: Kiani A 

PROVIDER: S-EPMC12118337 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature