{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T04:46:12Z","timestamp":1770525972392,"version":"3.49.0"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2002,3,1]],"date-time":"2002-03-01T00:00:00Z","timestamp":1014940800000},"content-version":"vor","delay-in-days":1124,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[1999,2]]},"abstract":"<jats:p>The enteropathogenic <jats:italic>Escherichia coli<\/jats:italic> (EPEC) Tir protein becomes tyrosine phosphorylated in host cells and displays an increase in apparent molecular mass. The interaction of Tir with the EPEC outer membrane protein, intimin, triggers actin nucleation beneath the adherent bacteria. The enterohaemorrhagic <jats:italic>E. coli<\/jats:italic> 0157:H7 (EHEC) Tir molecule is not tyrosine phosphorylated. In this paper, Tir tyrosine phosphorylation is shown to be essential for actin nucleation activity, but not for the increase in apparent molecular mass observed in target cells. Tyrosine phosphorylation had no role in Tir molecular mass shift, indicating additional host modifications. Analysis of Tir intermediates indicates that tyrosine\u2010independent modification functions to direct Tir's correct insertion from the cytoplasm into the host membrane. Deletion analysis identified Tir domains participating in translocation, association with the host membrane, modification and antibody recognition. Intimin was found to bind a 55\u2010amino\u2010acid region (TIBA) within Tir that topological and sequence analysis suggests is located in an extracellular loop. Homologous TIBA sequences exist in integrins, which also bind intimin. Collectively, this study provides definitive evidence for the importance of tyrosine phosphorylation for EPEC Tir function and reveals differences in the pathogenicity of EPEC and EHEC. The data also suggest a mechanism for Tir insertion into the host membrane, as well as providing clues to the mode of intimin\u2013integrin interaction.<\/jats:p>","DOI":"10.1046\/j.1365-2958.1999.01265.x","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T11:22:28Z","timestamp":1047468148000},"page":"1229-1241","source":"Crossref","is-referenced-by-count":208,"title":["Phosphorylation of tyrosine 474 of the enteropathogenic <i>Escherichia coli<\/i> (EPEC) Tir receptor molecule is essential for actin nucleating activity and is preceded by additional host modifications"],"prefix":"10.1111","volume":"31","author":[{"given":"Brendan","family":"Kenny","sequence":"first","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2002,3]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"crossref","first-page":"3547","DOI":"10.1128\/iai.65.9.3547-3555.1997","article-title":"Characterisation of two rabbit enteropathogenic E. coli (RDEC) secreted proteins, EspA and EspB, whose maximal secretion is sensitive to host body temperature","volume":"65","author":"Abe A.","year":"1997","journal-title":"Infect Immun"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.36.3.662-668.1998"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5340.1140"},{"key":"e_1_2_6_5_2","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1242\/jcs.102.3.427","article-title":"Differential expression of the VLA family of integrins along the crypt\u2013villus axis in the human small intestine","volume":"102","author":"Beaulieu J.\u2010F.","year":"1992","journal-title":"J Cell Sci"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.3.1237-1243.1998"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1998.00798.x"},{"key":"e_1_2_6_8_2","unstructured":"Donnenberg M.S.(1995) EnteropathogenicEscherichia coli. 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