Hyperactive PLCG1 drives non-canonical signaling to promote cell survival.

ABSTRACT: One of the long-standing questions in cell signaling field to identify and characterize key signaling nodes out of a complex network. Phospholipase Cγ1 (PLCG1) was identified as the most frequently mutated gene in adult T-cell leukemia/lymphoma, suggesting a critical function of PLCG1 in driving T cell activation. However, it remains unclear how these mutations regulate T cell physiology and pathology. Here we investigated three common leukemia/lymphoma associated mutations (R48W, S345F, and D1165H). We discovered that these mutations induced hyperactive T cell signaling and caused pro-survival phenotypes. PLCG1 mutants enhanced LAT condensation, calcium influx, and ERK activation. They promoted T cell proliferation, induced cell aggregation, and rendered resistance to vorinostat, a

SUBMITTER: Zeng L 

PROVIDER: S-EPMC11702640 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature