title: Phosphorylation control of protein tyrosine phosphatase A activity in Mycobacterium tuberculosis.
abstract: 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.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of British Columbia, Vancouver, BC V5Z 3J5, Canada; Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-environment and Bio-resource of the Three Gorges Area, Key Laboratory of Eco-environment of Three Gorges Reservoir, Ministry of Education, School of Life Sciences, Southwest University, Chongqing 400715, China; Institute of Ethnic-minority Medicine, School of Chemistry & Environmental Science, Guizhou Minzu University, Guiyang 550025, China.
authors.forename: Peifu
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-environment and Bio-resource of the Three Gorges Area, Key Laboratory of Eco-environment of Three Gorges Reservoir, Ministry of Education, School of Life Sciences, Southwest University, Chongqing 400715, China.
authors.forename: Wu
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of British Columbia, Vancouver, BC V5Z 3J5, Canada.
authors.forename: Dennis
authors.initials: D
authors.lastname: Wong
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-environment and Bio-resource of the Three Gorges Area, Key Laboratory of Eco-environment of Three Gorges Reservoir, Ministry of Education, School of Life Sciences, Southwest University, Chongqing 400715, China. Electronic address: georgex@swu.edu.cn.
authors.forename: Jianping
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of British Columbia, Vancouver, BC V5Z 3J5, Canada. Electronic address: yossi@mail.ubc.ca.
authors.forename: Yossef
authors.initials: Y
authors.lastname: Av-Gay
mesh_terms: D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000472:pathogenicity; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4 / Q000096:biosynthesis* / Q000378:metabolism; D014376:Tuberculosis / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D014443:Tyrosine / Q000378:metabolism
chemical_list: D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4
keywords: Mycobacterium tuberculosis; Phosphorylation; Protein kinase A; Protein tyrosine kinase A; Protein tyrosine phosphatase A