New PP1cδ splicing isoform induces G2/M arrest in intestinal epithelial cells by activating p38-MAPK

• 1、Cambridge-Suda (CAM-SU) Genomic Resource Center, Medical College of Soochow University, Soochow University 215123
• 2、Department of Oncology, The First Affiliated Hospital of Soochow University, Soochow University 215006

Abstract：The phosphorylation level of myosin light chain (MLC), which is essential for the regulation of epithelial tight junctional permeability, is balanced by myosin light chain kinase (MLCK) and myosin phosphatase activities. However, the expression and the function of PP1cδ, the catalytic subunit of myosin phosphatase, in intestinal epithelial cells have not been investigated. In this study, we identified a noval isoform of PP1cδ (PP1cδ short) in Caco-2BBe cells, which lacks 24-amino acids coding by exon 5 of the full length PP1cδ. In confluent Caco-2BBe cells, both PP1cδ isoforms are distributed at cell-cell contacts and colocalized with F-actin. Unlike the full length PP1cδ, the short isoform binds weakly to MYPT1. This study suggests that p38-MAPK may be a new substrate for MLCP holoenzyme. Overexpression of short PP1cδ inhibits the activity of MLCP holoenzyme, increasesthe phosphorylation level of p38-MAPK, thus causes G2/M arrest and inhibits mitosis. We also found that both full-length and short PP1cδ were simultaneously expressed in intestinal epitheliumunder normal physiological conditions. However, full-length PP1cδ was mainly expressed during regeneration of epithelium of micewith DSS treatment. Theswitchof PP1cδ isoforms may be associated withtheproliferation and repairof intestinal epithelialcells.

Keywords： cell biology PP1cδ isoform cell cycle p38-MAPK