Protein tyrosine phosphatase-PEST (PTP-PEST) regulates mast cell-activating signals in PTP activity-dependent and -independent manners

作者：Motohashi Satoru; Koizumi Karen; Honda Reika; Maruyama Atsuko; Palmer Helen E F; Mashima Keisuke^*

来源：Cellular Immunology, 2014, 289(1-2): 128-134.

DOI：10.1016/j.cellimm.2014.04.003

• Allergy
• Fc receptors
• Protein tyrosine phosphatase
• Signal transduction

Aggregation of the high-affinity IgE receptor (Fc epsilon RI) in mast cells leads to degranulation and production of numerous cytokines and lipid mediators that promote allergic inflammation. Tyrosine phosphorylation of proteins in response to Rai aggregation has been implicated in mast cell activation. Here, we determined the role of PTP-PEST (encoded by PTPN12) in the regulation of mast cell activation using the RBL-2H3 rat basophilic leukemia cell line as a model. PTP-PEST expression was significantly induced upon Fc epsilon Rl-crosslinking, and aggregation of Fc epsilon RI induced the phosphorylation of PTP-PEST at Ser39, thus resulting in the suppression of PTP activity. By overexpressing a phosphatase-dead mutant (PTP-PEST CS) and a constitutively active mutant (PTP-PEST SA) in RBL-2H3 cells, we showed that PTP-PEST decreased degranulation and enhanced IL-4 and IL-13 transcription in Fc epsilon RI-crosslinked RBL-2H3 cells, but PTP activity of PTP-PEST was not necessary for this regulation. However, Fc epsilon RI-induced TNF-alpha transcription was increased by the overexpression of PTP-PEST SA and suppressed by the overexpression of PTP-PEST CS. Taken together, these results suggest that PTP-PEST is involved in the regulation of Fc epsilon RI-mediated mast cell activation through at least two different processes represented by PTP activity-dependent and -independent pathways.

• 出版日期2014-6