title: Phosphorylation-mediated regulation of the Staphylococcus aureus secreted tyrosine phosphatase PtpA.
abstract: Due to the emergence of methicillin-resistant strains, Staphylococcus aureus has become as major public-health threat. Studies aimed at deciphering the molecular mechanism of virulence are thus required to identify new targets and develop efficient therapeutic agents. Protein phosphorylations are known to play key regulatory functions and their roles in pathogenesis are under intense scrutiny. Here we analyzed the protein tyrosine phosphatase PtpA of S. aureus, a member of the family of low molecular weight protein tyrosine phosphatases that are often secreted by pathogenic bacteria. We report for the first time that PtpA is phosphorylated in vitro by the S. aureus tyrosine kinase CapA1B2. A mass spectrometry approach allowed determining that Tyr122 and Tyr123 were the only two residues phosphorylated by this kinase. This result was confirmed by analysis of a double PtpA_Y122A/Y123A mutant that showed no phosphorylation by CapA1B2. Interestingly, PtpA phosphatase activity was abrogated in this mutant, suggesting a key regulatory function for these two tyrosine residues. This was further reinforced by the observation that CapA1B2-mediated phosphorylation significantly increased PtpA phosphatase activity. Moreover, we provide evidence that PtpA is secreted during growth of S. aureus. Together our results suggest that PtpA is an exported S. aureus signaling molecule controlled by tyrosine phosphorylation which may interfere with host cell signaling.
authors.affiliation: Laboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques, Université Montpellier 2, CNRS UMR 5235, Montpellier, France.
authors.forename: Solène
authors.initials: S
authors.lastname: Brelle
authors.affiliation: Laboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques, Université Montpellier 2, CNRS UMR 5235, Montpellier, France.
authors.forename: Grégory
authors.initials: G
authors.lastname: Baronian
authors.affiliation: Laboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques, Université Montpellier 2, CNRS UMR 5235, Montpellier, France.
authors.forename: Sylvaine
authors.initials: S
authors.lastname: Huc-Brandt
authors.affiliation: Laboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques, Université Montpellier 2, CNRS UMR 5235, Montpellier, France.
authors.forename: Laila Gannoun
authors.initials: LG
authors.lastname: Zaki
authors.affiliation: Centre de Biochimie Structurale, CNRS UMR 5048, INSERM U554, Université Montpellier I et II, Montpellier, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Cohen-Gonsaud
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Saarland, Homburg/Saar, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Bischoff
authors.affiliation: Laboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques, Université Montpellier 2, CNRS UMR 5235, Montpellier, France. Electronic address: virginie.molle@univ-montp2.fr.
authors.forename: Virginie
authors.initials: V
authors.lastname: Molle
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D049109:Cell Proliferation / Q000502:physiology; D010766:Phosphorylation / Q000502:physiology; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000201:enzymology*
chemical_list: D001426:Bacterial Proteins; D011505:Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases
keywords: Phosphorylation; Protein tyrosine phosphatase A; Secretion; Staphylococcus aureus; Tyrosine kinase