A streptococcal collagen-like protein interacts with the α2β1 integrin and induces intracellular signaling

Joseph O. Humtsoe, Jiyeun K. Kim, Yi Xu, Douglas R. Keene, Magnus Höök, Slawomir Lukomski, Kishore K. Wary

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

The streptococcal collagen-like proteins Scl1 and Scl2 are prokaryotic members of a large protein family with domains containing the repeating amino acid sequence (Gly-Xaa-Yaa)n that form a collagen-like triple-helical structure. Here, we test the hypothesis that Scl variant might interact with mammalian collagen-binding integrins. We show that the recombinant Scl protein p176 promotes adhesion and spreading of human lung fibroblast cells through an α2β1 integrin-mediated interaction as shown in cell adhesion inhibition assays using anti-α2β1 and anti-β1 integrins monoclonal antibodies. Accordingly, C2C12 cells stably expressing α2β1 integrin as the only collagen-binding integrin show productive cell adhesion activities on p176 that can be blocked by an anti-α2β1 integrin antibody. In addition, p176 promotes tyrosine phosphorylation of p125 FAK of C2C12 cells expressing α2β1 integrin, whereas parental C2C12 cells do not. Furthermore, adhesion of human lung fibroblast cells to p176 induces phosphorylation of p125FAK, p130CAS, and p68Paxillin proteins. In a domain swapping experiment, we show that integrin binds to the collagenous domain of the Scl protein. Moreover, the recombinant inserted domain of the α2 integrin interacts with p176 with a relatively high affinity (KD = 17 nM). Attempts to identify the integrin sites in p176 suggest that more than one site may be involved. These studies, for the first time, suggest that the collagen-like proteins of prokaryotes retained not only structural but also functional characteristics of their eukaryotic counterparts.

Original languageEnglish (US)
Pages (from-to)13848-13857
Number of pages10
JournalJournal of Biological Chemistry
Volume280
Issue number14
DOIs
StatePublished - Apr 8 2005

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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