FAK Structure and Regulation by Membrane Interactions and Force in Focal Adhesions
Open accessAbstract
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase with key roles in the regulation of cell adhesion migration, proliferation and survival. In cancer FAK is a major driver of invasion and metastasis and its upregulation is associated with poor patient prognosis. FAK is autoinhibited in the cytosol, but activated upon localisation into a protein complex, known as focal adhesion complex. This complex forms upon cell adhesion to the extracellular matrix (ECM) at the cytoplasmic side of the plasma membrane at sites of ECM attachment. FAK is anchored to the complex via multiple sites, including direct interactions with specific membrane lipids and connector proteins that attach focal adhesions to the actin cytoskeleton. In migrating cells, the contraction of actomyosin stress fibres attached to the focal adhesion complex apply a force to the complex, which is likely transmitted to the FAK protein, causing stretching of the FAK molecule. In this review we discuss the current knowledge of the FAK structure and how specific structural features are involved in the regulation of FAK signalling. We focus on two major regulatory mechanisms known to contribute to FAK activation, namely interactions with membrane lipids and stretching forces applied to FAK, and discuss how they might induce structural changes that facilitate FAK activation.
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The osteoclast cytoskeleton is made of four categories of filamentous structures and fulfills essential functions including cell adhesion, migration, contractility, division, vesicular transport, and bone resorption.
“The osteoclast cytoskeleton is made of filamentous structures that belong to one of four categories: polarized actin filaments; polarized microtubules; non-polarized intermediate filaments; or non-polarized septin filaments. The cytoskeleton fulfills essential functions including cell adhesion, migration, contractility, division, vesicular transport, and bone resorption [2,3,4,5,6].”
From Osteoclasts and Microgravity (2020) · cites this paper as [5]
The Introduction describes an actin-cytoskeleton connection that provides traction during cell migration as actomyosin fibres contract, supporting part of the functional claim. It does not address osteoclasts, the four filament categories, or the claimed roles in division, vesicular transport, and bone resorption. (LLM, conf=0.85)
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FAK activity sustains intrinsic and acquired ovarian cancer resistance to platinum chemotherapy
Diaz Osterman, C. J., Ozmadenci, D., Kleinschmidt, E. G., Taylor, K. N., Barrie, A. M., Jiang, S., Bean, L. M., Sulzmaier, F. J., Jean, C., Tancioni, I., et al. (2019) · eLife · doi:10.7554/elife.47327 · Cited by 145 · see citing works
The Rap1-RIAM-talin axis of integrin activation and blood cell function
Lagarrigue, F., Kim, C., & Ginsberg, M. H. (2016) · Blood · doi:10.1182/blood-2015-12-638700 · Cited by 143 · cited 1× · see citing works
“On the other hand, a high-affinity integrin state initiating ECM binding can be triggered by the binding of intracellular components, such as talin, kindlin, and RIAM [22,23].”
BackgroundCrystal Structure of the FERM Domain of Focal Adhesion Kinase
Ceccarelli, D. F. J., Song, H. K., Poy, F., Schaller, M. D., & Eck, M. J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m509188200 · Cited by 139 · cited 4× · see citing works
“Crystallised FERM domains contain most of the linker residues following the FERM domain (residues 362–399 or 362–405, [31]).”
BackgroundMethodInfluentialGoñi, G., Epifano, C., Boskovic, J., Camacho‐Artacho, M., Zhou, J., Bronowska, A. K., Martín, M. T., Eck, M. J., Kremer, L., Gräter, F., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1317022111 · Cited by 139 · cited 10× · see citing works
“mediated FAK activation is shown to be promoted by the plasma membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) [26].”
BackgroundInfluentialSelf-citationStructural and mechanistic insights into mechanoactivation of focal adhesion kinase
Bauer, M. S., Baumann, F., Daday, C., Redondo, P. N., Durner, E., Jobst, M. A., Milles, L. F., Mercadante, D., Pippig, D. A., Gaub, H. E., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1820567116 · Cited by 139 · cited 2× · see citing works
“Further, using atomic force microscopy (AFM) based single molecule force spectroscopy, it was shown that forces applied to FAK molecules via the KAKTLRK lipid binding site in the FERM domain and the C-terminus of the kinase domain (the FAT domain was not included in these studies) results in rupture of autoinhibitory…”
MethodSelf-citationChen, S.-Y., & Chen, H. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.02186-05 · Cited by 139 · cited 1× · see citing works
“This sequence is implicated in a number of interactions, including in binding to phosphorylated tails of the Met receptor [43], phosphoinositide lipids [25,26] (see Section 3), and via an intramolecular interaction to the C-terminal FAT domain [44] (see Section 2.”
BackgroundFAK dimerization controls its kinase‐dependent functions at focal adhesions
Brami‐Cherrier, K., Gervasi, N., Arsenieva, D., Walkiewicz, K. W., Boutterin, M., Ortega, Á., Leonard, P. G., Seantier, B., Gasmi, L., Bouceba, T., et al. (2014) · The EMBO Journal · doi:10.1002/embj.201386399 · Cited by 136 · cited 4× · see citing works
“These structures have defined the mechanism of FAK autoinhibition in the cytosol [35] and identified a number of interactions, including a mode of recruitment into focal adhesions via paxillin [53,54] and FERM mediated dimerization important for activation [44].”
BackgroundInfluentialCiobănaşu, C., Faivre, B., & Clainche, C. L. (2014) · Nature Communications · doi:10.1038/ncomms4095 · Cited by 134 · cited 1× · see citing works
“The stretching of talin is shown to reveal cryptic binding sites for vinculin, resulting in stabilization of the focal adhesion complex and a stronger attachment to actin [83,84].”
BackgroundMechanism of Focal Adhesion Kinase Mechanosensing
Zhou, J., Aponte-Santamaria, C. A., Sturm, S., Bullerjahn, J. T., Bronowska, A. K., & Gräter, F. (2015) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1004593 · Cited by 128 · cited 1× · see citing works
“In a separate study, atomistic molecular dynamics simulations were performed, starting from autoinhibited FAK bound via the KAKTLRK site to an explicit PIP2 containing membrane bilayer [89].”
MethodFERM Domain Interaction Promotes FAK Signaling
Dunty, J., Gabarra-Niecko, V., King, M. L., Ceccarelli, D. F. J., Eck, M. J., & Schaller, M. D. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.12.5353-5368.2004 · Cited by 120 · cited 2× · see citing works
“FAK mutated in the KAKTLRK sequence or FAK in PIP5KIγ knockdown cells still localise to focal adhesions, indicating that membrane interactions do not significantly contribute to FAK localisation [26,42].”
BackgroundLim, S., Chen, X. L., Tomar, A., Miller, N. L. G., Yoo, J., & Schlaepfer, D. D. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.129999 · Cited by 118 · see citing works
Structure of the Active N-terminal Domain of Ezrin
Smith, W. J., Nassar, N. N., Bretscher, A. P., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210601200 · Cited by 105 · cited 1× · see citing works
“The clover-leaf assembly of the FAK FERM domain is overall very similar to the one seen in the ERM family members ezrin [36], radixin [37], and moesin [38], but different to the FERM domain of talin, which surprisingly is found to arrange its lobes in a linear arrangement [39].”
BackgroundMolecular Recognition of Paxillin LD Motifs by the Focal Adhesion Targeting Domain
Hoellerer, M. K., Noble, M. E. M., Labesse, G., Campbell, I. D., Werner, J. M., & Arold, S. T. (2003) · Structure · doi:10.1016/j.str.2003.08.010 · Cited by 104 · cited 2× · see citing works
“These structures have defined the mechanism of FAK autoinhibition in the cytosol [35] and identified a number of interactions, including a mode of recruitment into focal adhesions via paxillin [53,54] and FERM mediated dimerization important for activation [44].”
BackgroundHunger‐Glaser, I., Salazar, E. P., Sinnett‐Smith, J. W., & Rozengurt, E. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210876200 · Cited by 102 · cited 3× · see citing works
“Subsequent studies have provided evidence for the propensity for this helix to detach from the four-helix bundle [56,57] and promote C-terminal phosphorylations on Y861, Y925 and S910 [58,59].”
BackgroundGrant, B. D., & Adams, J. A. (1996) · Biochemistry · doi:10.1021/bi952144+ · Cited by 95 · cited 1× · see citing works
“A likely explanation provides the study of Grant and Adams [79] showing that, in kinase/substrate complexes and if the enzyme/substrate ratio is close to one, phosphorylation rates are not determined by steady-state kinetics as seen in regular turnover kinetics.”
BackgroundGarces, C. A., Kurenova, E., Golubovskaya, V., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-1661 · Cited by 84 · see citing works
Gao, G., Prutzman, K. C., King, M. L., Scheswohl, D. M., DeRose, E. F., London, R. E., Schaller, M. D., & Campbell, S. L. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m309808200 · Cited by 81 · cited 3× · see citing works
“These structures have defined the mechanism of FAK autoinhibition in the cytosol [35] and identified a number of interactions, including a mode of recruitment into focal adhesions via paxillin [53,54] and FERM mediated dimerization important for activation [44].”
BackgroundDixon, R. D. S., Chen, Y., Ding, F., Khare, S. D., Prutzman, K. C., Schaller, M. D., Campbell, S. L., & Dokholyan, N. V. (2004) · Structure · doi:10.1016/j.str.2004.09.011 · Cited by 75 · cited 2× · see citing works
“Subsequent studies have provided evidence for the propensity for this helix to detach from the four-helix bundle [56,57] and promote C-terminal phosphorylations on Y861, Y925 and S910 [58,59].”
BackgroundWu, J.-C., Chen, Y., Kuo, C.-T., et al. (2015) · Scientific Reports · doi:10.1038/srep18476 · Cited by 64 · cited 1× · see citing works
“These interactions can contribute to Src activation and have been reported to recruit Src into focal adhesions [60].”
BackgroundPlaza-Menacho, I., Morandi, A., Mologni, L., Boender, P. J., Gambacorti-Passerini, C. B., Magee, A. I., Hofstra, R. M. W., Knowles, P. P., McDonald, N. Q., & Isacke, C. M. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.168500 · Cited by 63 · see citing works
Papusheva, E., de Queiroz, F. M., Dalous, J., et al. (2009) · Journal of Cell Science · doi:10.1242/jcs.028738 · Cited by 55 · cited 1× · see citing works
“Possibly, membrane binding was also the primary cause for a FRET change in a cellular study that used a similar FRET sensor but found that the sensor did not require FAK activity or autophosphorylation for an optimal FRET response upon localisation into focal adhesions [65].”
BackgroundYoon, S.-O., Shin, S., Karreth, F. A., Buel, G. R., Jedrychowski, M. P., Plas, D. R., Dedhar, S., Gygi, S. P., Roux, P. P., Dephoure, N., et al. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.06.033 · Cited by 53 · see citing works
Wang, Q., More, S. K., Vomhof‐DeKrey, E. E., Golovko, M. Y., & Basson, M. D. (2019) · Scientific Reports · doi:10.1038/s41598-019-51183-z · Cited by 41 · see citing works
Prutzman, K. C., Gao, G., King, M. L., et al. (2004) · Structure · doi:10.1016/j.str.2004.02.028 · Cited by 39 · cited 3× · see citing works
“Subsequent studies have provided evidence for the propensity for this helix to detach from the four-helix bundle [56,57] and promote C-terminal phosphorylations on Y861, Y925 and S910 [58,59].”
BackgroundMarlowe, T. A., Lenzo, F. L., Figel, S. A., et al. (2016) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-16-0366 · Cited by 38 · cited 1× · see citing works
“In oncogenic settings, and particular upon application of FAK inhibitors, it was shown that growth factor receptors can directly phosphorylate Y397 in FAK, thereby sustaining FAK scaffolding functions via phospho-Y397 even if FAK is efficiently inhibited [64].”
BackgroundKadaré, G., Gervasi, N., Brami‐Cherrier, K., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.593632 · Cited by 36 · cited 5× · see citing works
“To some extent this might promote dissociation of FAK from focal adhesions [58].”
BackgroundInfluentialYuan, C., Gou, X., Deng, J., Dong, Z., Ye, P., & Hu, Z. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.04.185 · Cited by 34 · see citing works
Structural Insights How PIP2 Imposes Preferred Binding Orientations of FAK at Lipid Membranes
Herzog, F. A., Braun, L., Schoen, I., & Viola Vogel, B. (2017) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.6b09349 · Cited by 31 · cited 1× · see citing works
“Coarse grain molecular dynamics simulations of autoinhibited FAK on a PIP2 membrane indicated that after membrane binding via the KAKTLRK sequence in the FERM domain the protein would rotate into two possible membrane bound states where FERM and kinase domains lie flat on the membrane with both domains bound to PIP2 […”
BackgroundZhou, Z., Feng, H., & Bai, Y. (2006) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.21107 · Cited by 30 · cited 2× · see citing works
“Subsequent studies have provided evidence for the propensity for this helix to detach from the four-helix bundle [56,57] and promote C-terminal phosphorylations on Y861, Y925 and S910 [58,59].”
BackgroundFragment-based discovery of focal adhesion kinase inhibitors.
Grädler, U., Bomke, J., Musil, D., Dresing, V., Lehmann, M., Hölzemann, G., Greiner, H., Esdar, C., Krier, M., & Heinrich, T. (2013) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2013.07.050 · Cited by 28 · cited 1× · see citing works
“Although a crystal structure of FAK in the “DFG-out” conformation exists bound to a type II inhibitor [45], it is not clear whether FAK adopts this conformation merely as a result of specific ligand interactions, or whether it might be part of a native regulation or catalytic cycle as proposed for other kinases includ…”
BackgroundD’Onofrio, P. M., Shabanzadeh, A. P., Choi, B., et al. (2019) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.18-25257 · Cited by 21 · see citing works
Marlowe, T. A., Dementiev, A., Figel, S. A., Rivera, A., Flavin, M. T., & Cance, W. G. (2019) · BMC Molecular and Cell Biology · doi:10.1186/s12860-019-0193-4 · Cited by 21 · cited 1× · see citing works
“Linker residues immediately following the FERM domain (368–375), including a PxxP motif known to constitute a binding site for the Src SH3 domain, are seen in two crystal structures to interact with the FERM F3 lobe and in one FERM molecule with the cleft between the F1 and F3 lobe [31,41].”
BackgroundExpression of Focal Adhesion Proteins in the Developing Rat Kidney
Matsuura, S., Kondo, S., Suga, K., Kinoshita, Y., Urushihara, M., & Kagami, S. (2011) · Journal of Histochemistry & Cytochemistry · doi:10.1369/0022155411413929 · Cited by 16 · see citing works
Phospholipid binding to the FAK catalytic domain impacts function
Hall, J. E., & Schaller, M. D. (2017) · PLoS ONE · doi:10.1371/journal.pone.0172136 · Cited by 7 · cited 3× · see citing works
“However, a second site on the kinase domain, that includes residues R508, K621 and K627, has recently been shown to also contribute to PIP2 binding [77].”
BackgroundInfluential
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Targeting PI3K/AKT signaling for treatment of idiopathic pulmonary fibrosis
Wang, J., Hu, K., Cai, X., Yang, B., He, Q., Wang, J., & Weng, Q. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.07.023 · Cited by 464 · see citing works
Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy
Huang, R., Chen, H., Liang, J., Li, Y., Yang, J., Luo, C., Tang, Y., Ding, Y., Liu, X., Yuan, Q., et al. (2021) · Journal of Cancer · doi:10.7150/jca.54699 · Cited by 218 · see citing works
“On the one hand, FAK can lead to focal adhesion, and actin stress fibers located on the inside of the cell membrane adhere to the focal adhesion spot [82].”
BackgroundRoles of focal adhesion proteins in skeleton and diseases
Chen, S., He, T., Zhong, Y., et al. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.09.020 · Cited by 152 · see citing works
PROTAC’ing oncoproteins: targeted protein degradation for cancer therapy
Kelm, J. M., Pandey, D. S., Malin, E., Kansou, H. W., Arora, S., Kumar, R., & Gavande, N. S. (2023) · Molecular Cancer · doi:10.1186/s12943-022-01707-5 · Cited by 115 · see citing works
Progress in the Development of Small Molecular Inhibitors of Focal Adhesion Kinase (FAK)
Lu, Y., & Sun, H. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01248 · Cited by 104 · see citing works
Effects of Mechanical Stress Stimulation on Function and Expression Mechanism of Osteoblasts
Liu, P., Tu, J., Wang, W., Li, Z., Li, Y., Yu, X., & Zhang, Z. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.830722 · Cited by 99 · see citing works
Integrin and Its Associated Proteins as a Mediator for Mechano-Signal Transduction
Katoh, K. (2025) · Biomolecules · doi:10.3390/biom15020166 · Cited by 105 · see citing works
“AT PPR 1, the tyrosine 397 residue is present, which is very crucial for the activation of FAK [104].”
Mechanochemistry: Fundamental Principles and Applications
Dong, L., Li, L., Chen, H., Cao, Y., & Lei, H. (2024) · Advanced Science · doi:10.1002/advs.202403949 · Cited by 99 · see citing works
Yang, J., Wang, P., Zhang, Y., Zhang, M., Sun, Q., Chen, H., Dong, L., Chu, Z., Xue, B., Hoff, W. D., et al. (2024) · Cell stem cell · doi:10.1016/j.stem.2024.09.016 · Cited by 95 · see citing works
Roles and inhibitors of FAK in cancer: current advances and future directions
Hu, H.-H., Wang, S., Shang, H.-L., Lv, H., Chen, B., Gao, S., & Chen, X. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1274209 · Cited by 91 · see citing works
New insights into FAK structure and function in focal adhesions
Coq, J. L., Acebrón, I., Martín, B. R., Navajas, P. L., & Lietha, D. (2022) · Journal of Cell Science · doi:10.1242/jcs.259089 · Cited by 79 · see citing works
Self-citationMechanical homeostasis imbalance in hepatic stellate cells activation and hepatic fibrosis
Zhao, Y.-Q., Deng, X.-W., Xu, G.-Q., Lin, J., Lu, H.-Z., & Chen, J. (2023) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2023.1183808 · Cited by 71 · see citing works
Extracellular Matrix Signaling Cues: Biological Functions, Diseases, and Therapeutic Targets
Zhao, T., Huang, Y., Zhu, J., Qin, Y., Wu, H., Yu, J., Zhai, Q., Li, S., Qin, X., Wang, D., et al. (2025) · MedComm · doi:10.1002/mco2.70281 · Cited by 77 · see citing works
Wang, S., Englund, E., Kjellman, P., Li, Z., Ahnlide, J. K., Rodriguez-Cupello, C., Saggioro, M., Kanzaki, R., Pietras, K., Lindgren, D., et al. (2021) · Nature Cell Biology · doi:10.1038/s41556-021-00702-0 · Cited by 67 · see citing works
RetractedResponse of mesenchymal stem cells to surface topography of scaffolds and the underlying mechanisms
Xiao, L., Sun, Y., Liao, L., & Su, X. (2023) · Journal of Materials Chemistry B · doi:10.1039/d2tb01875f · Cited by 68 · see citing works
A Hierarchical Mechanotransduction System: From Macro to Micro
Cao, R. Y., Tian, H., Tian, Y., & Fu, X. (2023) · Advanced Science · doi:10.1002/advs.202302327 · Cited by 63 · see citing works
Analytical methods in studying cell force sensing: principles, current technologies and perspectives
Liu, X., Yu, L., Xiao, A., Sun, W., Wang, H., Wang, X., Zhou, Y., Li, C., Li, J., Wang, Y., et al. (2025) · Regenerative Biomaterials · doi:10.1093/rb/rbaf007 · Cited by 54 · see citing works
Schmidt, A., Liebelt, G., Nießner, F., von Woedtke, T., & Bekeschus, S. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101809 · Cited by 53 · see citing works
Smith, J. K. (2020) · Life · doi:10.3390/life10090207 · Cited by 52 · see citing works
Pancreatic endocrine and exocrine signaling and crosstalk in physiological and pathological status
Hu, C., Chen, Y., Yin, X., Xu, R., Yin, C., Wang, C., & Zhao, Y. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02098-3 · Cited by 59 · see citing works
Focal Adhesion Kinase Fine Tunes Multifaced Signals toward Breast Cancer Progression
Rigiracciolo, D. C., Cirillo, F., Talia, M., Muglia, L., Gutkind, J. S., Maggiolini, M., & Lappano, R. (2021) · Cancers · doi:10.3390/cancers13040645 · Cited by 53 · see citing works
“It consists of an activation loop located at the 564–592 gene sequence and the conformation depends on the difference between the active and the inactive form of FAK [35,47].”
BackgroundInfluentialExtracellular Matrix Stiffness in Lung Health and Disease
Guo, T., He, C., Venado, A. E., & Zhou, Y. (2022) · Comprehensive physiology · doi:10.1002/cphy.c210032 · Cited by 100 · see citing works
Focal adhesion kinase (FAK): its structure, characteristics, and signaling in skeletal system
Huang, Y., Liao, J., Vlashi, R., & Chen, G. (2023) · Cellular Signalling · doi:10.1016/j.cellsig.2023.110852 · Cited by 49 · see citing works
Focal adhesion kinase: Insight into its roles and therapeutic potential in oesophageal cancer
Zhang, Y., Liu, S., Zhou, S. F., Yu, D., Gu, J., Qin, Q., Cheng, Y., & Sun, X. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.10.005 · Cited by 49 · see citing works
Liu, Y., Sun, L. J., Li, Y., & Holmes, C. A. (2024) · Journal of Extracellular Vesicles · doi:10.1002/jev2.12472 · Cited by 50 · see citing works
“Meanwhile, PTK2, also known as focal adhesion kinase (FAK), which is critical in cell attachment to the extracellular matrix (Tapial Martínez et al., 2020), was identified as the central node of passage-related protein differences in BMSC-EVs, with a 100-fold increase at P2 compared to P8, implying…”
BackgroundExtracellular Matrix Stiffness in Lung Health and Disease
Guo, T., He, C., Venado, A. E., & Zhou, Y. (2022) · Comprehensive physiology · doi:10.1002/j.2040-4603.2022.tb00222.x · Cited by 48 · see citing works
“The role of FAK in sensing mechanical force among other cues has been well characterized and reviewed elsewhere (377, 398).”
Cytoskeletal crosstalk: A focus on intermediate filaments
Pradeau-Phélut, L., & Etienne‐Manneville, S. (2024) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2024.102325 · Cited by 47 · see citing works
New Insights on the Nuclear Functions and Targeting of FAK in Cancer
Pomella, S., Cassandri, M., Braghini, M. R., Marampon, F., Alisi, A., & Rota, R. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23041998 · Cited by 46 · see citing works
“FAK’s structure includes three main domains: an N-terminal FERM (four-point—1, ezrin, radixin and moesin—domain, a central kinase domain followed and a C-terminal FAT (focal adhesion targeting) domain (reviewed in [13]) that are separated by three proline-rich regions (PR1-3) working as binding sites for the Src homol…”
BackgroundMousson, A., Legrand, M., Steffan, T., Vauchelles, R., Carl, P., Gies, J., Lehmann, M., Zuber, G., Mey, J. D., Dujardin, D., et al. (2021) · Cancers · doi:10.3390/cancers13081871 · Cited by 36 · see citing works
“Structurally, FAK is a 125 kDa protein that contains an N-terminal FERM domain, a central kinase domain, and a Cterminal domain which contains the focal adhesion targeting (FAT) site [9].”
BackgroundValdivia, A., Avalos, A. M., & Leyton, L. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1221306 · Cited by 39 · see citing works
Wang, Y., Shen, N., Yang, Y., Xia, Y., Zhang, W., Yu, L., Wang, Z., Yang, Z., & Wang, Z. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-023-01366-z · Cited by 43 · see citing works
“Integrin clustering causes FAK to be recruited to newly generated focal adhesion sites, and various downstream effectors are phosphorylated after FAK activation, resulting in angiogenesis, cell migration, and cell proliferation [16–19].”
BackgroundMillward, D. J. (2021) · Nutrients · doi:10.3390/nu13030729 · Cited by 42 · see citing works
Lin, C., He, Y., Feng, Q., Xu, K., Chen, Z., Tao, B., Li, X., Xia, Z., Jiang, H., & Cai, K. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2021.121235 · Cited by 36 · see citing works
Focal adhesion kinase inhibitors, a heavy punch to cancer
Wu, Y., Li, N., Ye, C., Jiang, X., Luo, H., Zhang, B., Zhang, Y., & Zhang, Q. (2021) · Discover Oncology · doi:10.1007/s12672-021-00449-y · Cited by 36 · see citing works
“phosphorylated and binds to the junction protein Grb2 to make FAK aggregate with integrins, while Tyr397 and Tyr 861 both could recruit other SH2 proteins [10].”
BackgroundLi, L., Li, Z., Lu, C., Li, J., Zhang, K., Lin, C., Tang, X., Liu, Z., Zhang, Y., Han, R., et al. (2022) · Communications Biology · doi:10.1038/s42003-022-03111-7 · Cited by 34 · see citing works
Role of αVβ3 in Prostate Cancer: Metastasis Initiator and Important Therapeutic Target
Tang, L., Xu, M. Q., Zhang, L., Qu, L., & Liu, X. (2020) · OncoTargets and Therapy · doi:10.2147/ott.s258252 · Cited by 31 · see citing works
Luo, Q.-Y., Zhou, S.-N., Pan, W., Sun, J., Yang, L., Zhang, L., Qiu, M., & Yang, D. (2020) · Biochemical Pharmacology · doi:10.1016/j.bcp.2020.114318 · Cited by 31 · see citing works
Luo, N., Cheng, W., Zhou, Y., Gu, B., Zhao, Z., & Zhao, Y. (2021) · Animals · doi:10.3390/ani11072132 · Cited by 31 · see citing works
Roles of Integrins in Gastrointestinal Cancer Metastasis
Hou, S., Wang, J., Li, W., Hao, X., & Hang, Q. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.708779 · Cited by 30 · see citing works
How cells sense and integrate information from different sources
Ullo, M. F., & Case, L. B. (2023) · WIREs Mechanisms of Disease · doi:10.1002/wsbm.1604 · Cited by 29 · see citing works
Eshaq, A. M., Flanagan, T. W., Hassan, S.-Y., Asheikh, S. A. A., Al-Amoudi, W. A., Santourlidis, S., Hassan, S.-L., Alamodi, M. O., Bendhack, M. L., Alamodi, M. O., et al. (2024) · Cancers · doi:10.3390/cancers16152754 · Cited by 30 · see citing works
“The C-terminal region of the Fak family possesses a region that is implicated in focal adhesion targeting (FAT) [124–126].”
BackgroundMedvedev, A. E., Kopylov, A. T., Бунеева, О. А., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21114187 · Cited by 29 · see citing works
Orthodontic Force–Induced BMAL1 in PDLCs Is a Vital Osteoclastic Activator
Xie, Y., Tang, Q., Yu, S., et al. (2021) · Journal of Dental Research · doi:10.1177/00220345211019949 · Cited by 28 · see citing works
“1F; Tapial Martínez et al. 2020). qRT-PCR and Western blotting were performed to detect the mRNA and protein levels of BMAL1 and its downstream molecules period 2 (PER2) and cryptochrome 1 (CRY1).”
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- Authors
- Tapial Martínez, P., López Navajas, P., & Lietha, D.
- Affiliations
- Centro de Investigaciones Biológicas (CIB), Spanish National Research Council (CSIC), Cell Signalling and Adhesion Group, 28040 Madrid, Spain
- Consejo Superior de Investigaciones Científicas (ES)
- Corresponding author
- Lietha, Daniel
- ORCID
- Lietha, Daniel
- Venue
- Biomolecules
- Publisher
- MDPI AG
- Published
- 2020-01-24
- Volume
- 10
- Issue
- 2
- Pages
- 179
- ISSN
- 2218-273X (ISSN-L)
- PMC
- PMC7072507
- OpenAlex
- W3002011373
- Semantic Scholar
- 3830912f29816d1795a68aeaa4e040c80c112f67
- Cited by
- 206
- References
- 95
- Citations by year
- 2026: 16 · 2025: 21 · 2024: 45 · 2023: 44 · 2022: 41 · 2021: 24 · 2020: 15
- FWCI
- 4.32
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Biomolecules (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Ministerio de Ciencia, Innovación y Universidades (RTI2018-099318-B-I00, RTI2018)
- Ministerio de Asuntos Económicos y Transformación Digital, Gobierno de España (BFU2016-77665-R)
- European Regional Development Fund (BFU2016, RTI2018, BFU2016-77665-R)
- Agencia Estatal de Investigación
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- focal adhesion kinase, focal adhesions, membrane lipid interactions, mechanical forces, FAK activation, non-receptor tyrosine kinase, cell adhesion, extracellular matrix, metastasis, actin cytoskeleton
- MeSH terms
- Cell Adhesion, Cell Movement, Humans, Membranes, Actin Cytoskeleton, Phosphorylation, Signal Transduction, Focal Adhesions, Mechanotransduction, Cellular, Focal Adhesion Kinase 1
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