An engineered viral protein activates STAT5 to prevent T cell suppression.

ABSTRACT: T cell therapy efficacy can be compromised if cytokine-induced Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling is dysregulated or insufficient to sustain functionality. Here, we demonstrate that LCK kinase activity can be recruited to noncanonical protein substrates to directly activate targeted STAT proteins in T cells. STAT activation was accomplished by engineering the herpesvirus saimiri tyrosine kinase interacting protein (TIP) to provide a platform for the enforced recruitment of LCK to STAT proteins. We determined that a minimal region of TIP that binds to LCK could be combined with STAT binding sites derived from endogenous cytokine receptors. These constructs activated targeted STAT proteins in a cytokine-independent manner. We identified a STA

SUBMITTER: Zheng Y 

PROVIDER: S-EPMC12863462 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature