Trends Biochem Sci. 2026 Oct 2:S0968-0004(26)00279-3. doi: 10.1016/j.tibs.2026.09.001. Online ahead of print.

ABSTRACT

Protein tyrosine phosphatases (PTPs) are increasingly recognized as regulators of signaling networks rather than mere antagonists of kinases. Interactome-level analyses reveal that many PTPs function as scaffolds that organize spatially constrained signaling complexes, thereby influencing context-dependent signaling outputs. Focusing on representative nonreceptor PTPs (SHP-2, PTPN23, and PTPN13) and receptor PTPs (PTPRM and PTPRK), this review integrates methodological advances that enable increasingly detailed mapping of PTP-centered interactomes. Across cancer, neurobiology, and immune signaling, changes in these assemblies link scaffold function to disease phenotypes. This framework highlights PTP scaffold functions beyond catalysis and emerging therapeutic strategies targeting protein-protein interactions and scaffold-dependent mechanisms.

PMID:42823268 | DOI:10.1016/j.tibs.2026.09.001