Details

Autor(en) / Beteiligte

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

Titel

A Streptococcal Collagen-like Protein Interacts with the alpha sub(2) beta sub(1) Integrin and Induces Intracellular Signaling

Ist Teil von

• The Journal of biological chemistry, 2005-04, Vol.280 (14), p.13848-13857

Erscheinungsjahr

2005

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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) sub(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 alpha sub(2) beta sub(1) integrin-mediated interaction as shown in cell adhesion inhibition assays using anti- alpha sub(2) beta sub(1) and anti- beta sub(1) integrins monoclonal antibodies. Accordingly, C2C12 cells stably expressing alpha sub(2) beta sub(1) integrin as the only collagen-binding integrin show productive cell adhesion activities on p176 that can be blocked by an anti- alpha sub(2) beta sub(1) integrin antibody. In addition, p176 promotes tyrosine phosphorylation of p125 super(FAK) of C2C12 cells expressing alpha sub(2) beta sub(1) integrin, whereas parental cells do not. Furthermore, C2C12 adhesion of human lung fibroblast cells to p176 induces phosphorylation of p125 super(FAK), p130 super(CAS), and p68 super(Paxillin) 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 alpha sub(2) integrin interacts with p176 with a relatively high affinity (K sub(D) = 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.