Decoding C‑SH2 Domain/Peptide Interactions in SH2 Domain-Containing Tyrosine Phosphatase 2: A Molecular Framework for Rational Inhibitor Design.

ABSTRACT: SH2 domain-containing tyrosine phosphatase 2 (SHP2), encoded by PTPN11, plays a crucial role in multiple cellular processes, including proliferation and differentiation. Mutations in PTPN11 are implicated in various developmental disorders and hematological diseases, while wild-type (WT) SHP2 is a pivotal target in cancer therapy. SHP2 comprises two Src-homology 2 domains (N-SH2 and C-SH2), followed by a protein tyrosine phosphatase (PTP) catalytic domain. Under basal conditions, the N-SH2 domain autoinhibits SHP2 by blocking access to the catalytic site. An allosteric transition controls the detachment of the N-SH2 domain from the active site (and thus catalytic activity) and the affinity of the N-SH2 domain for its binding partners. We recently introduced the inhibition of

SUBMITTER: Innamorati C 

PROVIDER: S-EPMC12878756 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature