Mechanisms of phosphorylation in colitis regulation: PP2Acα as an emerging therapeutic target for inflammatory bowel disease.

Post-translational modification(PTM) is the terminal regulatory step of gene expression, directly regulating protein function through reversible or irreversible chemical modifications, enabling cells to rapidly respond to internal and external environmental stimuli. Among various post-translational modifications (PTMs), the dynamic balance between phosphorylation and dephosphorylation constitutes the molecular switch for inflammatory signal transduction, and disruption of this balance is an important cause of the persistent non-healing of inflammatory bowel disease (IBD). The catalytic subunit of protein phosphatase 2 A, PP2Acα(encoded by the PPP2CA gene), as the predominant serine/threonine phosphatase in the body, accounts for more than 70% of serine/threonine phosphatase activity in mammalian tissues and has been proven to play a key role in inflammatory diseases such as rheumatoid arthritis. However, the specific regulatory network, targets, and mechanisms of PPP2CA in IBD have not yet been systematically elucidated. This review aims to summarize the regulatory role of PTMs (especially phosphorylation/dephosphorylation) in IBD, deeply explore the structure and function of PPP2CA and its potential mechanisms in intestinal inflammation, and propose core scientific questions for future research, providing a new theoretical perspective for IBD therapeutic strategies targeting PPP2CA.