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

Joel B. Heim, Cera A. McDonald, Saranya P. Wyles, Sindhuja Sominidi-Damodaran, Edwin J. Squirewell, Ming Li, Catherine Motsonelidze, Ralph T. Böttcher, Jan Van Deursen, Alexander Meves

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere0200558
JournalPLoS One
Volume13
Issue number7
DOIs
StatePublished - Jul 1 2018

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non-specific protein-tyrosine kinase
Focal Adhesion Protein-Tyrosine Kinases
Phosphorylation
protein phosphorylation
skin (animal)
Tyrosine
tyrosine
homeostasis
Skin
Homeostasis
mice
epidermis (animal)
Epidermis
mutation
glutamates
Glutamic Acid
phosphotransferases (kinases)
pregnancy
Pregnancy
Mutation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

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

FAK auto-phosphorylation site tyrosine 397 is required for development but dispensable for normal skin homeostasis. / Heim, Joel B.; McDonald, Cera A.; Wyles, Saranya P.; Sominidi-Damodaran, Sindhuja; Squirewell, Edwin J.; Li, Ming; Motsonelidze, Catherine; Böttcher, Ralph T.; Van Deursen, Jan; Meves, Alexander.

In: PLoS One, Vol. 13, No. 7, e0200558, 01.07.2018.

Research output: Contribution to journalArticle

Heim, JB, McDonald, CA, Wyles, SP, Sominidi-Damodaran, S, Squirewell, EJ, Li, M, Motsonelidze, C, Böttcher, RT, Van Deursen, J & Meves, A 2018, 'FAK auto-phosphorylation site tyrosine 397 is required for development but dispensable for normal skin homeostasis', PLoS One, vol. 13, no. 7, e0200558. https://doi.org/10.1371/journal.pone.0200558
Heim JB, McDonald CA, Wyles SP, Sominidi-Damodaran S, Squirewell EJ, Li M et al. FAK auto-phosphorylation site tyrosine 397 is required for development but dispensable for normal skin homeostasis. PLoS One. 2018 Jul 1;13(7). e0200558. https://doi.org/10.1371/journal.pone.0200558
Heim, Joel B. ; McDonald, Cera A. ; Wyles, Saranya P. ; Sominidi-Damodaran, Sindhuja ; Squirewell, Edwin J. ; Li, Ming ; Motsonelidze, Catherine ; Böttcher, Ralph T. ; Van Deursen, Jan ; Meves, Alexander. / FAK auto-phosphorylation site tyrosine 397 is required for development but dispensable for normal skin homeostasis. In: PLoS One. 2018 ; Vol. 13, No. 7.
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