Phosphorylation control of protein tyrosine phosphatase A activity in Mycobacterium tuberculosis

Protein tyrosine phosphatase A (PtpA) has been shown to play a key role in human macrophage infection by Mycobacterium tuberculosis (Mtb). Protein tyrosine kinase A (PtkA) was the first protein tyrosine kinase shown to phosphorylate PtpA. Here, we found that PtkA-mediated phosphorylation of PtPA on Tyr-128 and Tyr-129 enhances the PtPA phosphatase activity. Moreover, ex-vivo protein-protein interaction assays showed that PtpA can be phosphorylated by several eukaryotic-like Ser/Thr protein kinases, such as protein kinase A (PknA). PknA was found to regulate PtpA phosphatase activity through Thr-45 phosphorylation. These results indicate that members of two independent families of protein kinases tune PtpA activity in Mtb.