English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

FAK auto-phosphorylation site tyrosine 397 is required for development but dispensable for normal skin homeostasis

MPS-Authors
/persons/resource/persons77774

Böttcher,  Ralph T.
Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society;

External Resource
No external resources are shared
Fulltext (public)

journal.pone.0200558.pdf
(Publisher version), 10MB

Supplementary Material (public)
There is no public supplementary material available
Citation

Heim, J. B., McDonald, C. A., Wyles, S. P., Sominidi-Damodaran, S., Squirewel, E. J., Li, M., et al. (2018). FAK auto-phosphorylation site tyrosine 397 is required for development but dispensable for normal skin homeostasis. PLoS One, 13(7): e0200558. doi:10.1371/journal.pone.0200558.


Cite as: http://hdl.handle.net/21.11116/0000-0002-032B-B
Abstract
Focal adhesion kinase (FAK) is an intensely studied non-receptor tyrosine kinase with roles in cancer and other common human diseases. Despite the large interest in FAK, the in vivo contribution of FAK auto-phosphorylation site tyrosine (Y) 397 to FAK function is incompletely understood. To study FAK Y397 in vivo we analyzed mice with 'non-phosphorylatable' Y-to-phenylalanine (F) and `phospho-mimicking' Y-to-glutamate (E) mutations in the germline. We found that FAK Y397F mice die early during embryogenesis with abnormal angiogenesis like FAK kinase-dead mice. When Y397 is mutated to a glutamate mice survive beyond mid-gestation like mice where Y397 is lost by deletion of FAK exon 15. In culture, defects in proliferation, invasion and gene expression were more severe with the FAK Y397F than with the FAK Y397E mutation despite the inability of FAK Y397E to bind SRC. Conditional expression of FAK Y397F or Y397E in unchallenged avascular epidermis, however, resulted in no appreciable phenotype. We conclude that FAK Y397 is required for the highly dynamic tissue remodeling during development but dispensable for normal homeostasis of avascular epidermis. In contrast to the Y397F mutation, FAK Y397E retains sufficient biological activity to allow for development beyond mid-gestation.