The Ability of Protein Tyrosine Phosphatase SHP-1 to Suppress NFκB Can Be Inhibited by Dominant Negative Mutant of SIRPα

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Abstract
In contrast with hematopoietic cells and fibroblasts, which express mainly one form of protein tyrosine phosphatase (PTP) SHP-1 or SHP-2, epithelial cells like A431, HeLa, and 293 express both forms of PTP. These two PTP regulate NFκB activity differently; SHP-1 inhibits and SHP-2 stimulates NFκB activation. In epithelial cells the process of NFκB activation depends on the combination of two PTP activities. The activity of PTP SHP-1 dominates in this tandem according to our data. The signal regulatory protein (SIRPα) is the adapter and the substrate of PTP SHP-1 and SHP-2. We investigated the role of SIRPα and its dominant negative mutant in PTP activities in 293 cells. The overexpression of wild-type SIRPα suppresses the activities of both PTP, but has a stronger effect on PTP SHP-2, especially when this protein is overexpressed in 293 cells. In contrast with wild-type SIRPα, its dominant negative mutant acts predominantly against PTP SHP-1, and can be detected in the complex with PTP SHP-1. The expression of dominant negative mutant of SIRPα has an effect similar to the expression of dominant negative PTP SHP-1 in the process of NFκB activation.