A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Integrin α2β1 in nonactivated conformation can induce focal adhesion kinase signaling
Tekijät: Salmela Maria, Jokinen Johanna, Tiitta Silja, Rappu Pekka, Cheng Holland R, Heino Jyrki
Kustantaja: NATURE PUBLISHING GROUP
Julkaisuvuosi: 2017
Journal: Scientific Reports
Tietokannassa oleva lehden nimi: SCIENTIFIC REPORTS
Lehden akronyymi: SCI REP-UK
Artikkelin numero: ARTN 3414
Vuosikerta: 7
Sivujen määrä: 11
ISSN: 2045-2322
eISSN: 2045-2322
DOI: https://doi.org/10.1038/s41598-017-03640-w
Verkko-osoite: http://www.nature.com/articles/s41598-017-03640-w
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/23070272
Conformational activation of integrins is generally required for ligand binding and cellular signalling. However, we have previously reported that the nonactivated conformation of alpha 2 beta 1 integrin can also bind to large ligands, such as human echovirus 1. In this study, we show that the interaction between the nonactivated integrin and a ligand resulted in the activation of focal adhesion kinase (FAK) in a protein kinase C dependent manner. A loss-of-function mutation, alpha 2E336A, in the alpha 2-integrin did not prevent the activation of FAK, nor did EDTA-mediated inactivation of the integrin. Full FAK activation was observed, since phosphorylation was not only confirmed in residue Y397, but also in residues Y576/7. Furthermore, initiation of downstream signaling by paxillin phosphorylation in residue Y118 was evident, even though this activation was transient by nature, probably due to the lack of talin involvement in FAK activation and the absence of vinculin in the adhesion complexes formed by the nonactivated integrins. Altogether these results indicate that the nonactivated integrins can induce cellular signaling, but the outcome of the signaling differs from conventional integrin signaling.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
