Publication year
2017Source
Proceedings of the National Academy of Sciences USA, 114, 15, (2017), pp. 3933-3938ISSN
Publication type
Article / Letter to editor

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Organization
Cell Biology (UMC)
Journal title
Proceedings of the National Academy of Sciences USA
Volume
vol. 114
Issue
iss. 15
Page start
p. 3933
Page end
p. 3938
Subject
Radboudumc 19: Nanomedicine RIMLS: Radboud Institute for Molecular Life SciencesAbstract
Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase involved in development and human disease, including cancer. It is currently thought that the four-point one, ezrin, radixin, moesin (FERM)-kinase domain linker, which contains autophosphorylation site tyrosine (Y) 397, is not required for in vivo FAK function until late midgestation. Here, we directly tested this hypothesis by generating mice with FAK Y397-to-phenylalanine (F) mutations in the germline. We found that Y397F embryos exhibited reduced mesodermal fibronectin (FN) and osteopontin expression and died during mesoderm development akin to FAK kinase-dead mice. We identified myosin-1E (MYO1E), an actin-dependent molecular motor, to interact directly with the FAK FERM-kinase linker and induce FAK kinase activity and Y397 phosphorylation. Active FAK in turn accumulated in the nucleus where it led to the expression of osteopontin and other FN-type matrix in both mouse embryonic fibroblasts and human melanoma. Our data support a model in which FAK Y397 autophosphorylation is required for FAK function in vivo and is positively regulated by MYO1E.
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- Academic publications [202799]
- Faculty of Medical Sciences [80020]
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