Macromolecular crowding amplifies allosteric regulation of T-cell protein tyrosine phosphatase.

ABSTRACT: T-cell protein tyrosine phosphatase (TC-PTP) is a negative regulator of T-cell receptor and oncogenic receptor tyrosine kinase signaling and implicated in cancer and autoimmune disease. TC-PTP activity is modulated by an intrinsically disordered C-terminal region (IDR) and suppressed in cells under basal conditions. In vitro structural studies have shown that the dynamic reorganization of IDR around the catalytic domain, driven by electrostatic interactions, can lead to TC-PTP activity inhibition; however, the process has not been studied in cells. Here, by assessing a mutant (³⁷⁸KRKRPR³⁸³ mutated into ³⁷⁸EAAAPE³⁸³, called TC45^E/A) with impaired tail-PTP domain interaction, we obtained evidence that the downmodulation of TC-PTP enzymat

SUBMITTER: Tun MT 

PROVIDER: S-EPMC9720572 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature