Genomes and Genes
focal adhesion kinase 1
Summary: A non-receptor protein tyrosine kinase with PROTEIN PHOSPHATASE 1 regulatory activity that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION.
- Karna E, Szoka L, Palka J. Thrombin-dependent modulation of ?1-integrin-mediated signaling up-regulates prolidase and HIF-1? through p-FAK in colorectal cancer cells. Mol Cell Biochem. 2012;361:235-41 pubmed publisher..It was accompanied by increase in the expression of MAP kinases, ERK1 and ERK2. It suggests that integrin-dependent signaling through p-FAK is up-regulated in DLD-1 cells and it may represent potential target for anti-cancer therapy. ..
- Riopel M, Krishnamurthy M, Li J, Liu S, Leask A, Wang R. Conditional ?1-integrin-deficient mice display impaired pancreatic ? cell function. J Pathol. 2011;224:45-55 pubmed publisher..Our results demonstrate that ?1-integrin is involved in the regulation of glucose metabolism and contributes to the maintenance of ? cell survival and function in vivo. ..
- Hu X, Wei L, Taylor T, Wei J, Zhou X, Wang J, et al. Hypoxic preconditioning enhances bone marrow mesenchymal stem cell migration via Kv2.1 channel and FAK activation. Am J Physiol Cell Physiol. 2011;301:C362-72 pubmed publisher..These findings provide novel evidence that HP enhances the ability of BMSCs to migrate and home to the injured region; this effect is mediated through a regulatory role of Kv2.1 on FAK phosphorylation/activation. ..
- Mehta R, Yamada T, Taylor B, Christov K, King M, Majumdar D, et al. A cell penetrating peptide derived from azurin inhibits angiogenesis and tumor growth by inhibiting phosphorylation of VEGFR-2, FAK and Akt. Angiogenesis. 2011;14:355-69 pubmed publisher..This novel, direct antiangiogenic effect of p28 on endothelial cells may enhance the cell cycle inhibitory and apoptotic properties of this prototype peptide on tumor cell proliferation as it enters a Phase II clinical trial. ..
- Serrels A, Canel M, Brunton V, Frame M. Src/FAK-mediated regulation of E-cadherin as a mechanism for controlling collective cell movement: insights from in vivo imaging. Cell Adh Migr. 2011;5:360-5 pubmed..We focus on the regulatory crosstalk between the Src/FAK signaling axis and E-cadherin in vivo. ..
- Choi C, Webb B, Chimenti M, Jacobson M, Barber D. pH sensing by FAK-His58 regulates focal adhesion remodeling. J Cell Biol. 2013;202:849-59 pubmed publisher..These data are relevant to understanding cancer metastasis, which is dependent on increased pHi and FAK activity. ..
- Wei J, Wei L, Zhou X, Lu Z, Francis K, Hu X, et al. Formation of Kv2.1-FAK complex as a mechanism of FAK activation, cell polarization and enhanced motility. J Cell Physiol. 2008;217:544-57 pubmed publisher..1 expression and co-localization of Kv2.1 and FAK significantly enhanced directional cell migration and wound closure. It is suggested that the Kv2.1 channel may function as a promoting signal for FAK activation and cell motility. ..
- Izumchenko E, Singh M, Plotnikova O, Tikhmyanova N, Little J, Serebriiskii I, et al. NEDD9 promotes oncogenic signaling in mammary tumor development. Cancer Res. 2009;69:7198-206 pubmed publisher..This study provides the first in vivo evidence of a role for NEDD9 in breast cancer progression and suggests that NEDD9 expression may provide a biomarker for tumor aggressiveness. ..
- Evans N, Minelli C, Gentleman E, LaPointe V, Patankar S, Kallivretaki M, et al. Substrate stiffness affects early differentiation events in embryonic stem cells. Eur Cell Mater. 2009;18:1-13; discussion 13-4 pubmed
- Taubenberger A, Woodruff M, Bai H, Muller D, Hutmacher D. The effect of unlocking RGD-motifs in collagen I on pre-osteoblast adhesion and differentiation. Biomaterials. 2010;31:2827-35 pubmed publisher..Taken together, these quantitative insights reveal an approach for the development of alternative collagen I- based surfaces for tissue engineering applications. ..
- Song H, Cha M, Song B, Kim I, Chang W, Lim S, et al. Reactive oxygen species inhibit adhesion of mesenchymal stem cells implanted into ischemic myocardium via interference of focal adhesion complex. Stem Cells. 2010;28:555-63 pubmed publisher..These results indicate that ROS inhibit cellular adhesion of engrafted MSCs and provide evidence that the elimination of ROS might be a novel strategy for improving the survival of engrafted MSCs. ..
- Long W, Yi P, Amazit L, LaMarca H, Ashcroft F, Kumar R, et al. SRC-3Delta4 mediates the interaction of EGFR with FAK to promote cell migration. Mol Cell. 2010;37:321-32 pubmed publisher..Our study also reveals that a nuclear receptor coactivator can act in the periphery of a cell to directly mediate activation of an enzyme. ..
- Chen J, Tang Y, Huang S, Juan H, Wu L, Sun Y, et al. A novel sialyltransferase inhibitor suppresses FAK/paxillin signaling and cancer angiogenesis and metastasis pathways. Cancer Res. 2011;71:473-83 pubmed publisher..Lith-O-Asp is worthy for further testing as a novel antimetastasis drug for cancer treatment. ..
- Benoit Y, Larrivée J, Groulx J, Stankova J, Vachon P, Beaulieu J. Integrin alpha8beta1 confers anoikis susceptibility to human intestinal epithelial crypt cells. Biochem Biophys Res Commun. 2010;399:434-9 pubmed publisher..Consequently, alpha8beta1 is a prerequisite for the proper conduct of anoikis in normal HIECs, whereas its loss contributes to the illicit acquisition of anoikis resistance. ..
- Chan K, Bennin D, Huttenlocher A. Regulation of adhesion dynamics by calpain-mediated proteolysis of focal adhesion kinase (FAK). J Biol Chem. 2010;285:11418-26 pubmed publisher..Expression of wild-type but not calpain-resistant FAK rescues talin dynamics in FAK-deficient cells. Taken together, our findings suggest a novel role for calpain proteolysis of FAK in regulating adhesion dynamics in motile cells. ..
- Mitra A, Sawada K, Tiwari P, Mui K, Gwin K, Lengyel E. Ligand-independent activation of c-Met by fibronectin and ?(5)?(1)-integrin regulates ovarian cancer invasion and metastasis. Oncogene. 2011;30:1566-76 pubmed publisher..These data suggest that fibronectin promotes ovarian cancer invasion and metastasis through an ?(5)?(1)-integrin/c-Met/FAK/Src-dependent signaling pathway, transducing signals through c-Met in an HGF/SF-independent manner. ..
- Wen W, Chau E, Jackson Boeters L, Elliott C, Daley T, Hamilton D. TGF-ß1 and FAK regulate periostin expression in PDL fibroblasts. J Dent Res. 2010;89:1439-43 pubmed publisher..In conclusion, periostin protein is strongly expressed in the human PDL. In vitro, periostin mRNA levels are modulated by cyclic strain as well as TGF-?1 via FAK-dependent pathways...
- Chen T, Chan P, Chen C, Chen H. Phosphorylation of focal adhesion kinase on tyrosine 194 by Met leads to its activation through relief of autoinhibition. Oncogene. 2011;30:153-66 pubmed publisher..Collectively, this study provides the first example to explain how FAK is activated by receptor tyrosine kinases. ..
- Schaller M. Cellular functions of FAK kinases: insight into molecular mechanisms and novel functions. J Cell Sci. 2010;123:1007-13 pubmed publisher..This Commentary summarizes some of these recent discoveries that are relevant to the control of biological responses of the cell. ..
- Chauhan B, Disanza A, Choi S, Faber S, Lou M, Beggs H, et al. Cdc42- and IRSp53-dependent contractile filopodia tether presumptive lens and retina to coordinate epithelial invagination. Development. 2009;136:3657-67 pubmed publisher..Although invagination of the archenteron in sea urchins and dorsal closure in Drosophila are known to be partly dependent on filopodia, this mechanism of morphogenesis has not previously been identified in vertebrates. ..
- Meng X, Jin Y, Yu Y, Bai J, Liu G, Zhu J, et al. Characterisation of fibronectin-mediated FAK signalling pathways in lung cancer cell migration and invasion. Br J Cancer. 2009;101:327-34 pubmed publisher..Our data suggest that fibronectin-mediated activation of FAK that leads to lung cancer metastasis could occur through ERK or PI3K/Akt regulation of MMP9/calpain-2 or MMP9/RhoA activity, respectively. ..
- Tan T, Lai C, Huang C, Yang W, Chen H, Hsu H, et al. CTGF enhances migration and MMP-13 up-regulation via alphavbeta3 integrin, FAK, ERK, and NF-kappaB-dependent pathway in human chondrosarcoma cells. J Cell Biochem. 2009;107:345-56 pubmed publisher..Taken together, our results indicated that CTGF enhances the migration of chondrosarcoma cells by increasing MMP-13 expression through the alphavbeta3 integrin, FAK, ERK, and NF-kappaB signal transduction pathway. ..
- Zhang X, Jiang G, Cai Y, Monkley S, Critchley D, Sheetz M. Talin depletion reveals independence of initial cell spreading from integrin activation and traction. Nat Cell Biol. 2008;10:1062-8 pubmed publisher..We suggest that talin is not required for initial cell spreading. However, talin provides the important mechanical linkage between ligand-bound integrins and the actin cytoskeleton required to catalyse focal adhesion-dependent pathways. ..
- Luo M, Fan H, Nagy T, Wei H, Wang C, Liu S, et al. Mammary epithelial-specific ablation of the focal adhesion kinase suppresses mammary tumorigenesis by affecting mammary cancer stem/progenitor cells. Cancer Res. 2009;69:466-74 pubmed publisher..Together, these results show a novel function of FAK in maintaining the mammary cancer stem/progenitor cell population and provide a novel mechanism by which FAK may promote breast cancer development and progression...
- Behmoaram E, Bijian K, Jie S, Xu Y, Darnel A, Bismar T, et al. Focal adhesion kinase-related proline-rich tyrosine kinase 2 and focal adhesion kinase are co-overexpressed in early-stage and invasive ErbB-2-positive breast cancer and cooperate for breast cancer cell tumorigenesis and invasiveness. Am J Pathol. 2008;173:1540-50 pubmed publisher..Together, these data support the cooperative function of Pyk2 and FAK in breast cancer progression and suggest that dual inhibition of FAK and Pyk2 is an efficient therapeutic approach for targeting invasive breast cancer. ..
- Alexander N, Branch K, Parekh A, Clark E, Iwueke I, Guelcher S, et al. Extracellular matrix rigidity promotes invadopodia activity. Curr Biol. 2008;18:1295-1299 pubmed publisher..These data suggest a potential mechanism, via invadopodia, for the reported correlation of tissue density with cancer aggressiveness...
- Papadopoulou N, Charalampopoulos I, Alevizopoulos K, Gravanis A, Stournaras C. Rho/ROCK/actin signaling regulates membrane androgen receptor induced apoptosis in prostate cancer cells. Exp Cell Res. 2008;314:3162-74 pubmed publisher..Our findings suggest that Rho small GTPases are major membrane androgen receptor effectors controlling actin reorganization and apoptosis in prostate cancer cells. ..
- Vultur A, Buettner R, Kowolik C, Liang W, Smith D, Boschelli F, et al. SKI-606 (bosutinib), a novel Src kinase inhibitor, suppresses migration and invasion of human breast cancer cells. Mol Cancer Ther. 2008;7:1185-94 pubmed publisher..Our findings indicate that SKI-606 inhibits signaling pathways involved in controlling tumor cell motility and invasion, suggesting that SKI-606 is a promising therapeutic for breast cancer. ..
- Beierle E, Massoll N, Hartwich J, Kurenova E, Golubovskaya V, Cance W, et al. Focal adhesion kinase expression in human neuroblastoma: immunohistochemical and real-time PCR analyses. Clin Cancer Res. 2008;14:3299-305 pubmed publisher..These novel findings provide evidence that FAK is expressed by advanced-stage neuroblastoma and provide a rationale for targeting FAK in the treatment of this tumor. ..
- Ossovskaya V, Lim S, Ota N, Schlaepfer D, Ilic D. FAK nuclear export signal sequences. FEBS Lett. 2008;582:2402-6 pubmed publisher..Although, both NES1 and NES2 are evolutionary conserved, and present as well in FAK-related protein kinase Pyk2, only NES2 demonstrates full biological nuclear export activity. ..
- Lim S, Mikolon D, Stupack D, Schlaepfer D. FERM control of FAK function: implications for cancer therapy. Cell Cycle. 2008;7:2306-14 pubmed..We discuss how the pharmacological inhibition of FAK kinase activity may impact tumor progression through combined effects of blocking both tumor- and stromal-associated signaling regulating neo-vascularization. ..
- Park E, Park M, Lee S, Li Y, Kim J, Lee J, et al. Cholesterol depletion induces anoikis-like apoptosis via FAK down-regulation and caveolae internalization. J Pathol. 2009;218:337-49 pubmed publisher..Our results suggest that the cholesterol content and/or surface levels of the caveolae affect the activity of FAK, which in turn regulates caveolae internalization and cell survival. ..
- Nakamura J, Shigematsu S, Yamauchi K, Takeda T, Yamazaki M, Kakizawa T, et al. Biphasic function of focal adhesion kinase in endothelial tube formation induced by fibril-forming collagens. Biochem Biophys Res Commun. 2008;374:699-703 pubmed publisher..In conclusion, our data indicate that FAK is functioning in cell migration, but fibril-forming collagen-induced FAK degradation is necessary for endothelial tube formation. ..
- Xu B, Song G, Ju Y, Li X, Song Y, Watanabe S. RhoA/ROCK, cytoskeletal dynamics, and focal adhesion kinase are required for mechanical stretch-induced tenogenic differentiation of human mesenchymal stem cells. J Cell Physiol. 2012;227:2722-9 pubmed publisher..This work provides novel insights regarding the mechanisms of tenogenesis in a stretch-induced environment and supports the therapeutic potential of hMSCs...
- Luo X, Zhou W, Tao Y, Wang X, Li D. TLR4 Activation Promotes the Secretion of IL-8 Which Enhances the Invasion and Proliferation of Endometrial Stromal Cells in an Autocrine Manner via the FAK Signal Pathway. Am J Reprod Immunol. 2015;74:467-79 pubmed publisher..IL-8 could enhance the invasion and proliferation of ESCs through the FAK signal pathway, and these effects could be abolished by an anti-CXCL8 neutralizing antibody or by a FAK inhibitor. ..
- Slanina H, Hebling S, Hauck C, Schubert Unkmeir A. Cell invasion by Neisseria meningitidis requires a functional interplay between the focal adhesion kinase, Src and cortactin. PLoS ONE. 2012;7:e39613 pubmed publisher..A cooperative interplay between FAK, Src and cortactin then enables endocytosis of N. meningitidis into host cells. ..
- Rangaswami H, Schwappacher R, Tran T, Chan G, Zhuang S, Boss G, et al. Protein kinase G and focal adhesion kinase converge on Src/Akt/?-catenin signaling module in osteoblast mechanotransduction. J Biol Chem. 2012;287:21509-19 pubmed publisher..These data explain how mechanical stimulation of osteoblasts leads to increased signaling through a growth regulatory pathway essential for maintaining skeletal integrity. ..
- Yang H, Yu C, Yang Z. N-acetylglucosaminyltransferase V negatively regulates integrin ?5?1-mediated monocyte adhesion and transmigration through vascular endothelium. Int J Oncol. 2012;41:589-98 pubmed publisher..These effects promoted FAK-mediated downstream signaling, including the ERK pathway, and indicate that GnT-V may be a potential therapeutic target for vascular inflammatory conditions. ..
- Lim S, Miller N, Chen X, Tancioni I, Walsh C, Lawson C, et al. Nuclear-localized focal adhesion kinase regulates inflammatory VCAM-1 expression. J Cell Biol. 2012;197:907-19 pubmed publisher..These studies reveal new developmental and anti-inflammatory roles for kinase-inhibited FAK in limiting VCAM-1 production via nuclear localization and promotion of GATA4 turnover. ..
- Herzog B, Pellet Many C, Britton G, Hartzoulakis B, Zachary I. VEGF binding to NRP1 is essential for VEGF stimulation of endothelial cell migration, complex formation between NRP1 and VEGFR2, and signaling via FAK Tyr407 phosphorylation. Mol Biol Cell. 2011;22:2766-76 pubmed publisher..Identification of key residues essential for VEGF binding and biological functions provides the basis for a rational design of antagonists of VEGF binding to NRP1. ..
- Wang S, Rath P, Lal B, Richard J, Li Y, Goodwin C, et al. EphB2 receptor controls proliferation/migration dichotomy of glioblastoma by interacting with focal adhesion kinase. Oncogene. 2012;31:5132-43 pubmed publisher..These novel findings suggest that tumor cell invasion can be therapeutically targeted by inhibiting EphB2 signaling, and that optimal antitumor responses to EphB2 targeting may require concurrent use of anti-proliferative agents. ..
- Wu H, Teng P, Jayaraman T, Onishi S, Li J, Bannon L, et al. Dentin matrix protein 1 (DMP1) signals via cell surface integrin. J Biol Chem. 2011;286:29462-9 pubmed publisher..Rauch, F., Davis, S. I., Zhang, S., Rios, H., Drezner, M. K., Quarles, L. D., Bonewald, L. F., and White, K. E. (2006) Nat. Genet. 38, 1310-1315) it can be hypothesized that DMP1 could be a key effector of ECM-osteocyte signaling. ..
- Carter C. Multiplexed high content screening reveals that cigarette smoke condensate-altered cell signaling pathways are accentuated through FAK inhibition in human bronchial cells. Int J Toxicol. 2012;31:257-66 pubmed publisher..CSC exerts changes in BEAS-2B cells by altering morphology and activating MAPK pathways. ..
- Jeong Y, Park W, Kim M, Baek K, Kwon N, Yun H, et al. Leucine-rich glioma inactivated 3 promotes HaCaT keratinocyte migration. Wound Repair Regen. 2013;21:634-40 pubmed publisher..Overall, these data suggest that LGI3 stimulates HaCaT cell migration following ?-catenin accumulation through the Akt pathway. ..
- Chu M, Iyengar R, Koshman Y, Kim T, Russell B, Martin J, et al. Serine-910 phosphorylation of focal adhesion kinase is critical for sarcomere reorganization in cardiomyocyte hypertrophy. Cardiovasc Res. 2011;92:409-19 pubmed publisher..FAK undergoes S910 phosphorylation via PKC? and Src-dependent pathways that are important for cell spreading and sarcomere reorganization. Reduced FAK-S910 phosphorylation may contribute to sarcomere disorganization in DCM. ..
- Huang W, Chan S, Jang T, Chang J, Ko Y, Yen T, et al. miRNA-491-5p and GIT1 serve as modulators and biomarkers for oral squamous cell carcinoma invasion and metastasis. Cancer Res. 2014;74:751-64 pubmed publisher..Together, our findings identify a functional axis for OSCC invasion that suggests miR-491-5p and GIT1 as biomarkers for prognosis in this cancer. ..
- Zheng Y, Yang W, Xia Y, Hawke D, Liu D, Lu Z. Ras-induced and extracellular signal-regulated kinase 1 and 2 phosphorylation-dependent isomerization of protein tyrosine phosphatase (PTP)-PEST by PIN1 promotes FAK dephosphorylation by PTP-PEST. Mol Cell Biol. 2011;31:4258-69 pubmed publisher..These findings uncover an important mechanism for the regulation of PTP-PEST in activated Ras-induced tumor progression. ..