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doi: 10.1242/10.1242/jcs.00373


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Journal of Cell Science 116, 1409-1416 (2003)
doi: 10.1242/jcs.00373


Commentary

Focal adhesion kinase: the first ten years

J. Thomas Parsons

Department of Microbiology, Box 800734, University of Virginia Health System, Charlottesville, VA 22908, USA

e-mail: jtp{at}virginia.edu

The protein tyrosine kinase focal adhesion kinase (FAK) plays a prominent role in integrin signaling. FAK activation, demonstrated by an increase in phosphorylation of Tyr397 as well as other sites in the protein, is best understood in the context of the engagement of integrins at the cell surface. Activation of FAK results in recruitment of a number of SH2-domain- and SH3-domain-containing proteins, which mediate signaling to several downstream pathways. FAK-dependent activation of these pathways has been implicated in a diverse array of cellular processes, including cell migration, growth factor signaling, cell cycle progression and cell survival.

Key words: Kinase, Focal Adhesion, Migration, Cytoskeleton


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S. Itoh, A. Taketomi, S. Tanaka, N. Harimoto, Y.-i. Yamashita, S.-i. Aishima, T. Maeda, K. Shirabe, M. Shimada, and Y. Maehara
Role of Growth Factor Receptor Bound Protein 7 in Hepatocellular Carcinoma
Mol. Cancer Res., July 1, 2007; 5(7): 667 - 673.
[Abstract] [Full Text] [PDF]


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EndocrinologyHome page
I. Ihnatovych, W. Hu, J. L. Martin, A. T. Fazleabas, P. de Lanerolle, and Z. Strakova
Increased Phosphorylation of Myosin Light Chain Prevents in Vitro Decidualization
Endocrinology, July 1, 2007; 148(7): 3176 - 3184.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
D. D. Schlaepfer, S. Hou, S.-T. Lim, A. Tomar, H. Yu, Y. Lim, D. A. Hanson, S. A. Uryu, J. Molina, and S. K. Mitra
Tumor Necrosis Factor-{alpha} Stimulates Focal Adhesion Kinase Activity Required for Mitogen-activated Kinase-associated Interleukin 6 Expression
J. Biol. Chem., June 15, 2007; 282(24): 17450 - 17459.
[Abstract] [Full Text] [PDF]


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Mol. Biol. CellHome page
S. Liu, X. Shi-wen, L. Kennedy, D. Pala, Y. Chen, M. Eastwood, D. E. Carter, C. M. Black, D. J. Abraham, and A. Leask
FAK Is Required for TGFbeta-induced JNK Phosphorylation in Fibroblasts: Implications for Acquisition of a Matrix-remodeling Phenotype
Mol. Biol. Cell, June 1, 2007; 18(6): 2169 - 2178.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
J. K. Slack-Davis, K. H. Martin, R. W. Tilghman, M. Iwanicki, E. J. Ung, C. Autry, M. J. Luzzio, B. Cooper, J. C. Kath, W. G. Roberts, et al.
Cellular Characterization of a Novel Focal Adhesion Kinase Inhibitor
J. Biol. Chem., May 18, 2007; 282(20): 14845 - 14852.
[Abstract] [Full Text] [PDF]


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GENES CELLSHome page
M. Ozaki, H. Ogita, and Y. Takai
Involvement of integrin-induced activation of protein kinase C in the formation of adherens junctions
Genes Cells, May 1, 2007; 12(5): 651 - 662.
[Abstract] [Full Text] [PDF]


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DevelopmentHome page
S. Murakami, D. Umetsu, Y. Maeyama, M. Sato, S. Yoshida, and T. Tabata
Focal adhesion kinase controls morphogenesis of the Drosophila optic stalk
Development, April 15, 2007; 134(8): 1539 - 1548.
[Abstract] [Full Text] [PDF]


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Circ. Res.Home page
W. T. Gerthoffer
Mechanisms of Vascular Smooth Muscle Cell Migration
Circ. Res., March 16, 2007; 100(5): 607 - 621.
[Abstract] [Full Text] [PDF]


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Sci SignalHome page
Y.-l. Wang
Flux at Focal Adhesions: Slippage Clutch, Mechanical Gauge, or Signal Depot
Sci. Signal., March 13, 2007; 2007(377): pe10 - pe10.
[Abstract] [Full Text] [PDF]


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Infect. Immun.Home page
K. M. Bourzac, C. M. Botham, and K. Guillemin
Helicobacter pylori CagA Induces AGS Cell Elongation through a Cell Retraction Defect That Is Independent of Cdc42, Rac1, and Arp2/3
Infect. Immun., March 1, 2007; 75(3): 1203 - 1213.
[Abstract] [Full Text] [PDF]


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J. Virol.Home page
A. J. Pruijssers and M. R. Strand
PTP-H2 and PTP-H3 from Microplitis demolitor Bracovirus Localize to Focal Adhesions and Are Antiphagocytic in Insect Immune Cells
J. Virol., February 1, 2007; 81(3): 1209 - 1219.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
J. H. Lorch, T. O. Thomas, and H.-J. Schmoll
Bortezomib Inhibits Cell-Cell Adhesion and Cell Migration and Enhances Epidermal Growth Factor Receptor Inhibitor-Induced Cell Death in Squamous Cell Cancer
Cancer Res., January 15, 2007; 67(2): 727 - 734.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. K. Quadri and J. Bhattacharya
Resealing of endothelial junctions by focal adhesion kinase
Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L334 - L342.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
M. Takeji, T. Moriyama, S. Oseto, N. Kawada, M. Hori, E. Imai, and T. Miwa
Smooth Muscle {alpha}-Actin Deficiency in Myofibroblasts Leads to Enhanced Renal Tissue Fibrosis
J. Biol. Chem., December 29, 2006; 281(52): 40193 - 40200.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
Y. Zhao, S. Itoh, X. Wang, T. Isaji, E. Miyoshi, Y. Kariya, K. Miyazaki, N. Kawasaki, N. Taniguchi, and J. Gu
Deletion of Core Fucosylation on {alpha}3beta1 Integrin Down-regulates Its Functions
J. Biol. Chem., December 15, 2006; 281(50): 38343 - 38350.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
M. Kurayoshi, N. Oue, H. Yamamoto, M. Kishida, A. Inoue, T. Asahara, W. Yasui, and A. Kikuchi
Expression of Wnt-5a Is Correlated with Aggressiveness of Gastric Cancer by Stimulating Cell Migration and Invasion
Cancer Res., November 1, 2006; 66(21): 10439 - 10448.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Renal Physiol.Home page
H. Xu, L. Zeng, H. Peng, S. Chen, J. Jones, T.-L. Chew, M. M. Sadeghi, Y. S. Kanwar, and F. R. Danesh
HMG-CoA reductase inhibitor simvastatin mitigates VEGF-induced "inside-out" signaling to extracellular matrix by preventing RhoA activation
Am J Physiol Renal Physiol, November 1, 2006; 291(5): F995 - F1004.
[Abstract] [Full Text] [PDF]


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Mol. Biol. CellHome page
J. Shi and J. E. Casanova
Invasion of Host Cells by Salmonella typhimurium Requires Focal Adhesion Kinase and p130Cas
Mol. Biol. Cell, November 1, 2006; 17(11): 4698 - 4708.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
K. Yokouchi, Y. Numaguchi, R. Kubota, M. Ishii, H. Imai, R. Murakami, Y. Ogawa, T. Kondo, K. Okumura, D. E. Ingber, et al.
l-Caldesmon Regulates Proliferation and Migration of Vascular Smooth Muscle Cells and Inhibits Neointimal Formation After Angioplasty
Arterioscler Thromb Vasc Biol, October 1, 2006; 26(10): 2231 - 2237.
[Abstract] [Full Text] [PDF]


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Circ. Res.Home page
L. A. DiMichele, J. T. Doherty, M. Rojas, H. E. Beggs, L. F. Reichardt, C. P. Mack, and J. M. Taylor
Myocyte-Restricted Focal Adhesion Kinase Deletion Attenuates Pressure Overload-Induced Hypertrophy
Circ. Res., September 15, 2006; 99(6): 636 - 645.
[Abstract] [Full Text] [PDF]


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J EndocrinolHome page
A. Beardsley, D. M Robertson, and L. O'Donnell
A complex containing {alpha}6{beta}1-integrin and phosphorylated focal adhesion kinase between Sertoli cells and elongated spermatids during spermatid release from the seminiferous epithelium.
J. Endocrinol., September 1, 2006; 190(3): 759 - 770.
[Abstract] [Full Text] [PDF]


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CarcinogenesisHome page
T. C. Sroka, M. E. Pennington, and A. E. Cress
Synthetic D-amino acid peptide inhibits tumor cell motility on laminin-5
Carcinogenesis, September 1, 2006; 27(9): 1748 - 1757.
[Abstract] [Full Text] [PDF]


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J. Cell Sci.Home page
N. Desban, J.-C. Lissitzky, P. Rousselle, and J.-L. Duband
{alpha}1{beta}1-integrin engagement to distinct laminin-1 domains orchestrates spreading, migration and survival of neural crest cells through independent signaling pathways
J. Cell Sci., August 1, 2006; 119(15): 3206 - 3218.
[Abstract] [Full Text] [PDF]


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Mol. Biol. CellHome page
F. Le Boeuf, F. Houle, M. Sussman, and J. Huot
Phosphorylation of Focal Adhesion Kinase (FAK) on Ser732 Is Induced by Rho-dependent Kinase and Is Essential for Proline-rich Tyrosine Kinase-2-mediated Phosphorylation of FAK on Tyr407 in Response to Vascular Endothelial Growth Factor
Mol. Biol. Cell, August 1, 2006; 17(8): 3508 - 3520.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
Y. Sakamoto, H. Ogita, T. Hirota, T. Kawakatsu, T. Fukuyama, M. Yasumi, N. Kanzaki, M. Ozaki, and Y. Takai
Interaction of Integrin {alpha}vbeta3 with Nectin: IMPLICATION IN CROSS-TALK BETWEEN CELL-MATRIX AND CELL-CELL JUNCTIONS
J. Biol. Chem., July 14, 2006; 281(28): 19631 - 19644.
[Abstract] [Full Text] [PDF]


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Mol. Cell. Biol.Home page
S.-Y. Chen and H.-C. Chen
Direct Interaction of Focal Adhesion Kinase (FAK) with Met Is Required for FAK To Promote Hepatocyte Growth Factor-Induced Cell Invasion
Mol. Cell. Biol., July 1, 2006; 26(13): 5155 - 5167.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
N. N. Mon, H. Hasegawa, A. A. Thant, P. Huang, Y. Tanimura, T. Senga, and M. Hamaguchi
A Role for Focal Adhesion Kinase Signaling in Tumor Necrosis Factor-{alpha}-Dependent Matrix Metalloproteinase-9 Production in a Cholangiocarcinoma Cell Line, CCKS1.
Cancer Res., July 1, 2006; 66(13): 6778 - 6784.
[Abstract] [Full Text] [PDF]


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EndocrinologyHome page
K. Shiraishi and M. Ascoli
Activation of the Lutropin/Choriogonadotropin Receptor in MA-10 Cells Stimulates Tyrosine Kinase Cascades that Activate Ras and the Extracellular Signal Regulated Kinases (ERK1/2)
Endocrinology, July 1, 2006; 147(7): 3419 - 3427.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
J. S. Swaney, H. H. Patel, U. Yokoyama, B. P. Head, D. M. Roth, and P. A. Insel
Focal Adhesions in (Myo)fibroblasts Scaffold Adenylyl Cyclase with Phosphorylated Caveolin
J. Biol. Chem., June 23, 2006; 281(25): 17173 - 17179.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
J. H. Kim, H.-w. Kim, H. Jeon, P.-G. Suh, and S. H. Ryu
Phospholipase D1 Regulates Cell Migration in a Lipase Activity-independent Manner
J. Biol. Chem., June 9, 2006; 281(23): 15747 - 15756.
[Abstract] [Full Text] [PDF]


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J. Pharmacol. Exp. Ther.Home page
K. He, J. Huang, C. F. Lagenaur, and E. Aizenman
Methylisothiazolinone, A Neurotoxic Biocide, Disrupts the Association of Src Family Tyrosine Kinases with Focal Adhesion Kinase in Developing Cortical Neurons
J. Pharmacol. Exp. Ther., June 1, 2006; 317(3): 1320 - 1329.
[Abstract] [Full Text] [PDF]


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Clin. Cancer Res.Home page
P. M.F. Siesser and S. K. Hanks
The Signaling and Biological Implications of FAK Overexpression in Cancer.
Clin. Cancer Res., June 1, 2006; 12(11): 3233 - 3237.
[Full Text] [PDF]


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J. Virol.Home page
M. J. Bouchard, L. Wang, and R. J. Schneider
Activation of Focal Adhesion Kinase by Hepatitis B Virus HBx Protein: Multiple Functions in Viral Replication
J. Virol., May 1, 2006; 80(9): 4406 - 4414.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Cell Physiol.Home page
R. Eisen, S. Walid, D. R. Ratcliffe, and G. K. Ojakian
Regulation of epithelial tubule formation by Rho family GTPases
Am J Physiol Cell Physiol, May 1, 2006; 290(5): C1297 - C1309.
[Abstract] [Full Text] [PDF]


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Clin. Cancer Res.Home page
B. Gabriel, A. zur Hausen, E. Stickeler, C. Dietz, G. Gitsch, D.-C. Fischer, J. Bouda, C. Tempfer, and A. Hasenburg
Weak Expression of Focal Adhesion Kinase (pp125FAK) in Patients with Cervical Cancer Is Associated with Poor Disease Outcome
Clin. Cancer Res., April 15, 2006; 12(8): 2476 - 2483.
[Abstract] [Full Text] [PDF]




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