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Tyrosine phosphate hydrolysis of host proteins by an essential Yersinia virulence determinant

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America; (United States)
;  [1]; ;  [2]
  1. Stanford Univ., CA (United States)
  2. Purdue Univ., West Lafayette, IN (United States)

The plasmid-encoded YopH protein is a protein-tyrosine phosphatase that is essential for Yersinia virulence. The authors have investigated the molecular basis for the role of PTPase activity in Yersinia pathogenesis. Allelic recombination was employed to introduce a defined mutation in to the yopH plasmid gene. Conversion of the essential Cys-403 to Ala in the catalytic domain of the protein abolished YopH PTPase activity and significantly reduced the virulence of Yersinia pseudotuberculosis in a murine infection model. {sup 32}P-labeled phosphotyrosine-containing proteins were immunoprecipitated from extracts of Y. pseudotuberculosis-infected cell monolayers and analyzed by SDS/PAGE to assess the impact of YopH on host protein phosphorylation. Major proteins of 200, 120, and 60 kDa were dephosphorylated in macrophages associated with wild-type Y.pseydotuberculosis. Selective removal of phosphate from the 120- and 60-kDa proteins was shown to be specific to the YopH PTPase activity. These observations indicate that the essential function of YopH in Yersinia pathogenesis is host-protein dephosphorylation.

OSTI ID:
6045637
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 88:4; ISSN 0027-8424; ISSN PNASA
Country of Publication:
United States
Language:
English