The PTPRT pseudo-phosphatase domain is a denitrase

Protein tyrosine nitration occurs under both physiological and pathological conditions. However, enzymes that remove this protein modification have not yet been identified. Here we report that the pseudo-phosphatase domain of protein tyrosine receptor T (PTPRT) is a denitrase that removes nitro-groups from tyrosine residues in paxillin. PTPRT normally functions as a tumor suppressor and is frequently mutated in a variety of human cancers including colorectal cancer. We demonstrate that some of the tumor-derived mutations located in the pseudo-phosphatase domain impair the denitrase activity. Moreover, PTPRT mutant mice that inactivate the denitrase activity are susceptible to carcinogen-induced colon tumor formation. This study uncovers a novel enzymatic activity that is involved in tumor suppression.