New insights into FAK structure and function in focal adhesions
- PMID: 36239192
- DOI: 10.1242/jcs.259089
New insights into FAK structure and function in focal adhesions
Abstract
Focal adhesion kinase (FAK; also known as PTK2) was discovered three decades ago and is now recognised as a key player in the regulation of cell-matrix adhesion and mesenchymal cell migration. Although it is essential during development, FAK also drives invasive cancer progression and metastasis. On a structural level, the basic building blocks of FAK have been described for some time. However, a picture of how FAK integrates into larger assemblies in various cellular environments, including one of its main cellular locations, the focal adhesion (FA) complex, is only beginning to emerge. Nano-resolution data from cellular studies, as well as atomic structures from reconstituted systems, have provided first insights, but also point to challenges that remain for obtaining a full structural understanding of how FAK is integrated in the FA complex and the structural changes occurring at different stages of FA maturation. In this Review, we discuss the known structural features of FAK, the interactions with its partners within the FA environment on the cell membrane and propose how its initial assembly in nascent FAs might change during FA maturation under force.
Keywords: Cell adhesion; FAK; Focal adhesion kinase; Function; Structure.
© 2022. Published by The Company of Biologists Ltd.
Conflict of interest statement
Competing interests The authors declare no competing or financial interests.
Similar articles
-
Polarized focal adhesion kinase activity within a focal adhesion during cell migration.Nat Chem Biol. 2023 Dec;19(12):1458-1468. doi: 10.1038/s41589-023-01353-y. Epub 2023 Jun 22. Nat Chem Biol. 2023. PMID: 37349581 Free PMC article.
-
Calcium rises locally trigger focal adhesion disassembly and enhance residency of focal adhesion kinase at focal adhesions.J Biol Chem. 2004 Jul 2;279(27):28715-23. doi: 10.1074/jbc.M404054200. Epub 2004 Apr 21. J Biol Chem. 2004. PMID: 15102844
-
FAK displacement from focal adhesions: a promising strategy to target processes implicated in cancer progression and metastasis.Cell Commun Signal. 2021 Jan 7;19(1):3. doi: 10.1186/s12964-020-00671-1. Cell Commun Signal. 2021. PMID: 33413438 Free PMC article.
-
FAK Structure and Regulation by Membrane Interactions and Force in Focal Adhesions.Biomolecules. 2020 Jan 24;10(2):179. doi: 10.3390/biom10020179. Biomolecules. 2020. PMID: 31991559 Free PMC article. Review.
-
Control of motile and invasive cell phenotypes by focal adhesion kinase.Biochim Biophys Acta. 2004 Jul 5;1692(2-3):77-102. doi: 10.1016/j.bbamcr.2004.04.008. Biochim Biophys Acta. 2004. PMID: 15246681 Review.
Cited by
-
Focal adhesion kinase regulates tendon cell mechanoresponse and physiological tendon development.FASEB J. 2024 Sep;38(17):e70050. doi: 10.1096/fj.202400151R. FASEB J. 2024. PMID: 39259535
-
Cas phosphorylation regulates focal adhesion assembly.Elife. 2023 Jul 25;12:e90234. doi: 10.7554/eLife.90234. Elife. 2023. PMID: 37489578 Free PMC article.
-
Mechanical homeostasis imbalance in hepatic stellate cells activation and hepatic fibrosis.Front Mol Biosci. 2023 Apr 20;10:1183808. doi: 10.3389/fmolb.2023.1183808. eCollection 2023. Front Mol Biosci. 2023. PMID: 37152902 Free PMC article. Review.
-
Roles and inhibitors of FAK in cancer: current advances and future directions.Front Pharmacol. 2024 Feb 12;15:1274209. doi: 10.3389/fphar.2024.1274209. eCollection 2024. Front Pharmacol. 2024. PMID: 38410129 Free PMC article. Review.
-
Autophagy Modulates the Migration of Retinal Pericytes Induced by Advanced Glycation End Products.Evid Based Complement Alternat Med. 2022 Dec 14;2022:2760537. doi: 10.1155/2022/2760537. eCollection 2022. Evid Based Complement Alternat Med. 2022. PMID: 36569344 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous