title: Staphylococcal superantigen-like protein 8 (SSL8) binds to tenascin C and inhibits tenascin C-fibronectin interaction and cell motility of keratinocytes.
abstract: Staphylococcal superantigen-like protein (SSL), a family of exotoxins composed of 14 SSLs, exhibits no superantigenic activity despite of its structural similarity with superantigens. Several SSLs have been revealed to bind to host immune molecules such as IgA, IgG, complement and cell surface molecules expressed on immune cells, but the physiological function of SSL family has not been fully identified. In this study we attempted to isolate host target proteins of SSLs from human breast milk using SSLs-conjugated Sepharose. SSL8-conjugated Sepharose specifically recovered tenascin C (TNC), a multimodular and multifunctional extracellular matrix protein. Pull down analysis using SSL8-conjugated Sepharose and recombinant truncated fragments of TNC revealed that SSL8 interacts with fibronectin (FN) type III repeats 1-5 of TNC. The interaction of TNC with immobilized FN was attenuated, the scratch wound closure by HaCaT human keratinocytes was delayed and the inhibition of cell spreading on FN by TNC was recovered in the presence of SSL8. These findings suggest that SSL8 binds to TNC, thereby inhibits the TNC-FN interaction and motility of keratinocytes. The present study added a novel role of SSL family protein as an interrupting molecule against the function of extracellular matrix.
authors.affiliation: Department of Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1, Tanabe-Dori, Nagoya 467-8603, Japan. s-itoh@phar.nagoya-cu.ac.jp
authors.forename: Saotomo
authors.initials: S
authors.lastname: Itoh
authors.forename: Natsuko
authors.initials: N
authors.lastname: Yamaoka
authors.forename: Go
authors.initials: G
authors.lastname: Kamoshida
authors.forename: Takemasa
authors.initials: T
authors.lastname: Takii
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Tsuji
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Hayashi
authors.forename: Kikuo
authors.initials: K
authors.lastname: Onozaki
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D002465:Cell Movement; D005098:Exotoxins / Q000378:metabolism*; D005260:Female; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000276:immunology / Q000502:physiology*; D008895:Milk, Human / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology* / Q000378:metabolism* / Q000472:pathogenicity; D018089:Superantigens / Q000378:metabolism*; D019063:Tenascin / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing
chemical_list: D005098:Exotoxins; D005353:Fibronectins; D011994:Recombinant Proteins; D018089:Superantigens; D019063:Tenascin