Genomes and Genes
focal adhesion protein tyrosine kinases
Summary: A family of non-receptor, PROLINE-rich protein-tyrosine kinases.
- Saravanan C, Liu F, Gipson I, Panjwani N. Galectin-3 promotes lamellipodia formation in epithelial cells by interacting with complex N-glycans on alpha3beta1 integrin. J Cell Sci. 2009;122:3684-93 pubmed publisher..We propose that Gal-3 promotes epithelial cell migration by cross-linking MGAT5-modified complex N-glycans on alpha3beta1 integrin and subsequently activating alpha3beta1-integrin-Rac1 signaling to promote lamellipodia formation. ..
- Piao Y, Lu L, de Groot J. AMPA receptors promote perivascular glioma invasion via beta1 integrin-dependent adhesion to the extracellular matrix. Neuro Oncol. 2009;11:260-73 pubmed publisher..Together, these results suggest that AMPARs may link signals from the ECM to sites of FA, where signal integration promotes tumor invasion. ..
- Zheng Y, Xia Y, Hawke D, Halle M, Tremblay M, Gao X, et al. FAK phosphorylation by ERK primes ras-induced tyrosine dephosphorylation of FAK mediated by PIN1 and PTP-PEST. Mol Cell. 2009;35:11-25 pubmed publisher..These findings uncover the importance of sequential modification of FAK-by serine phosphorylation, isomerization, and tyrosine dephosphorylation--in the regulation of FAK activity and, thereby, in Ras-related tumor metastasis. ..
- Gao J, McConnell M, Yu B, Li J, Balko J, Black E, et al. MUC1 is a downstream target of STAT3 and regulates lung cancer cell survival and invasion. Int J Oncol. 2009;35:337-45 pubmed..MUC1 appears to be a cooperating oncoprotein with multiple oncogenic tyrosine kinase pathways and could be an effective target for the treatment of lung cancer. ..
- Lee D, Li Y, Chang S, Zhou J, Ho H, Chiu J, et al. Oscillatory flow-induced proliferation of osteoblast-like cells is mediated by alphavbeta3 and beta1 integrins through synergistic interactions of focal adhesion kinase and Shc with phosphatidylinositol 3-kinase and the Akt/mTOR/p70S6K pathway. J Biol Chem. 2010;285:30-42 pubmed publisher
- Yan L, Lin B, Zhu L, Hao Y, Qi Y, Wang C, et al. Enhancement of the adhesive and spreading potentials of ovarian carcinoma RMG-1 cells due to increased expression of integrin alpha5beta1 with the Lewis Y-structure on transfection of the alpha1,2-fucosyltransferase gene. Biochimie. 2010;92:852-7 pubmed publisher..Thus, Le(Y) in integrin alpha5beta1 was thought to be involved in the enhanced cell adhesion properties of malignant ovarian carcinomas. ..
- Ning L, Chen H, Kunnimalaiyaan M. Focal adhesion kinase, a downstream mediator of Raf-1 signaling, suppresses cellular adhesion, migration, and neuroendocrine markers in BON carcinoid cells. Mol Cancer Res. 2010;8:775-82 pubmed publisher..Our results showed for the first time that FAK is an essential downstream effector of the Raf-1/MEK1/2/ERK1/2 signaling cascade and negatively regulated the neuroendocrine and metastatic phenotype in BON cells. ..
- Schweppe R, Kerege A, French J, Sharma V, Grzywa R, Haugen B. Inhibition of Src with AZD0530 reveals the Src-Focal Adhesion kinase complex as a novel therapeutic target in papillary and anaplastic thyroid cancer. J Clin Endocrinol Metab. 2009;94:2199-203 pubmed publisher..Inhibition of the Src-FAK complex represents a promising therapeutic strategy for patients with advanced thyroid cancer, and phospho-FAK represents a potential biomarker for response. ..
- Dun Z, Zhang X, An J, Zheng L, Barrett R, Xie S. Specific shRNA targeting of FAK influenced collagen metabolism in rat hepatic stellate cells. World J Gastroenterol. 2010;16:4100-6 pubmed..000). These data support the hypothesis that shRNA-mediated disruption of FAK expression could attenuate extracellular matrix (ECM) synthesis and promote ECM degradation, making FAK a potential target for novel anti-fibrosis therapies. ..
- Pat B, Chen Y, Killingsworth C, Gladden J, Shi K, Zheng J, et al. Chymase inhibition prevents fibronectin and myofibrillar loss and improves cardiomyocyte function and LV torsion angle in dogs with isolated mitral regurgitation. Circulation. 2010;122:1488-95 pubmed publisher..The greater effect of CI on epicardial versus endocardial titin and noncollagen cell surface proteins may be responsible for the increase in torsion angle in chronic MR. ..
- Frame M, Patel H, Serrels B, Lietha D, Eck M. The FERM domain: organizing the structure and function of FAK. Nat Rev Mol Cell Biol. 2010;11:802-14 pubmed publisher..Importantly, the FAK FERM domain might act as a paradigm for the actions of other FERM domain-containing proteins. ..
- Xu Y, Wang H, Yan J, Sun X, Guo J, Zhu C. Antibody binding to cell surface amyloid precursor protein induces neuronal injury by deregulating the phosphorylation of focal adhesion signaling related proteins. Neurosci Lett. 2009;465:276-81 pubmed publisher..In addition, pretreatment with PTX and PP2 was able to suppress APP-antibody induced neuronal injury. Taken together, the results suggest a novel mechanism for APP mediating neuronal injury through deregulating FA signals. ..
- Lee S, Lee Y, Song C, Ahn Y, Han H. Role of FAK phosphorylation in hypoxia-induced hMSCS migration: involvement of VEGF as well as MAPKS and eNOS pathways. Am J Physiol Cell Physiol. 2010;298:C847-56 pubmed publisher..The results indicate that hypoxia increases migration of hMSCs via VEGF-mediated FAK phospholylation and involves the cooperative activity of the ROS, MAPK, eNOS and HIF-1alpha pathways. ..
- Laragione T, Gulko P. mTOR regulates the invasive properties of synovial fibroblasts in rheumatoid arthritis. Mol Med. 2010;16:352-8 pubmed publisher..This discovery suggests that rapamycin could have a role in RA therapy aimed at reducing the articular damage and erosive changes mediated by FLS. ..
- Chao W, Ashcroft F, Daquinag A, Vadakkan T, Wei Z, Zhang P, et al. Type I phosphatidylinositol phosphate kinase beta regulates focal adhesion disassembly by promoting beta1 integrin endocytosis. Mol Cell Biol. 2010;30:4463-79 pubmed publisher..Together, our findings identify PIPKIbeta as a novel regulator of focal adhesion disassembly and suggest that PIPKIbeta spatially regulates integrin endocytosis at adhesion sites to control cell migration. ..
- Michael K, Dumbauld D, Burns K, Hanks S, Garcia A. Focal adhesion kinase modulates cell adhesion strengthening via integrin activation. Mol Biol Cell. 2009;20:2508-19 pubmed publisher..This work demonstrates a novel role for FAK in integrin activation and the time-dependent generation of cell-ECM forces. ..
- Stylianou P, Skourides P. Imaging morphogenesis, in Xenopus with Quantum Dot nanocrystals. Mech Dev. 2009;126:828-41 pubmed publisher..These results provide new insights about the role of FAK and of focal adhesions during gastrulation and provide a new tool for the study of morphogenesis in vivo. ..
- Srinivasan R, Zabuawala T, Huang H, Zhang J, Gulati P, Fernandez S, et al. Erk1 and Erk2 regulate endothelial cell proliferation and migration during mouse embryonic angiogenesis. PLoS ONE. 2009;4:e8283 pubmed publisher..The regulation of Paxillin and Focal Adhesion Kinase expression occurred post-transcriptionally. These results demonstrate that ERK1 and ERK2 coordinate endothelial cell proliferation and migration during angiogenesis. ..
- Brezillon S, Radwanska A, Zeltz C, Malkowski A, Ploton D, Bobichon H, et al. Lumican core protein inhibits melanoma cell migration via alterations of focal adhesion complexes. Cancer Lett. 2009;283:92-100 pubmed publisher..Therefore, the cytoskeleton remodeling and the decreased pFAK phosphorylation induced by lumican in melanoma cells might explain, at least in part, the anti-invasive effect of this SLRP. ..
- Xia J, Lv N, Hong Y, Li C, Tao X, Chen X, et al. Increased expression of focal adhesion kinase correlates with cellular proliferation and apoptosis during 4-nitroquinoline-1-oxide-induced rat tongue carcinogenesis. J Oral Pathol Med. 2009;38:524-9 pubmed publisher..959, P < 0.05). Our results implicated a role for FAK in oral carcinogenesis. Inhibition of FAK might be a potential novel treatment strategy in this disease. ..
- Trimmer C, Whitaker Menezes D, Bonuccelli G, Milliman J, Daumer K, Aplin A, et al. CAV1 inhibits metastatic potential in melanomas through suppression of the integrin/Src/FAK signaling pathway. Cancer Res. 2010;70:7489-99 pubmed publisher..Furthermore, CAV1 expression markedly reduces the expression of integrin ?(3) in B16F10 melanoma cells. In summary, our findings provide experimental evidence that CAV1 may function as an antimetastatic gene in malignant melanoma. ..
- Klossner S, Durieux A, Freyssenet D, Flueck M. Mechano-transduction to muscle protein synthesis is modulated by FAK. Eur J Appl Physiol. 2009;106:389-98 pubmed publisher..The findings identify FAK as an upstream element of the mechano-sensory pathway of p70S6K activation whose Akt-independent regulation intervenes in control of muscle mass by mechanical stimuli in humans. ..
- Kapoor G, O Rourke D. SIRPalpha1 receptors interfere with the EGFRvIII signalosome to inhibit glioblastoma cell transformation and migration. Oncogene. 2010;29:4130-44 pubmed publisher..Further understanding of the molecular interactions between the SIRPalpha1 inhibitory receptor and the EGFRvIII signalosome may facilitate the identification of novel targets to inhibit the EGFRvIII glioblastoma phenotype. ..
- Jan Y, Ko B, Hsu C, Chang T, Chen S, Wang J, et al. Overexpressed focal adhesion kinase predicts a higher incidence of extrahepatic metastasis and worse survival in hepatocellular carcinoma. Hum Pathol. 2009;40:1384-90 pubmed publisher..Focal adhesion kinase is thus considered as a reasonable target for novel therapies against hepatocellular carcinoma progression and metastasis. ..
- Kweh F, Zheng M, Kurenova E, Wallace M, Golubovskaya V, Cance W. Neurofibromin physically interacts with the N-terminal domain of focal adhesion kinase. Mol Carcinog. 2009;48:1005-17 pubmed publisher..Thus, the results demonstrate the novel interaction of neurofibromin and FAK and suggest their involvement in cell adhesion, cell growth, and other cellular events and pathways. ..
- Li G, Jin R, Norris R, Zhang L, Yu S, Wu F, et al. Periostin mediates vascular smooth muscle cell migration through the integrins alphavbeta3 and alphavbeta5 and focal adhesion kinase (FAK) pathway. Atherosclerosis. 2010;208:358-65 pubmed publisher..These results reveal a mechanism whereby PN mediates vascular SMC migration through an interaction with alphaV-integrins (mainly alphanubeta3) and subsequent activation of FAK pathway. ..
- Kurenova E, Hunt D, He D, Magis A, Ostrov D, Cance W. Small molecule chloropyramine hydrochloride (C4) targets the binding site of focal adhesion kinase and vascular endothelial growth factor receptor 3 and suppresses breast cancer growth in vivo. J Med Chem. 2009;52:4716-24 pubmed publisher..Our data demonstrate that the FAK-VEGFR-3 interaction can be targeted by small druglike molecules and this interaction can provide the basis for highly specific novel cancer therapeutics...
- Gjorevski N, Nelson C. Endogenous patterns of mechanical stress are required for branching morphogenesis. Integr Biol (Camb). 2010;2:424-34 pubmed publisher..These data suggest that the pattern and magnitude of mechanical stress across epithelial tissues cooperate with biochemical signals to specify branching pattern. ..
- Kim J, Ahn S, Ko Y, Boo Y, Chi S, Ni C, et al. X-linked inhibitor of apoptosis protein controls alpha5-integrin-mediated cell adhesion and migration. Am J Physiol Heart Circ Physiol. 2010;299:H300-9 pubmed publisher..The findings of this study provide us with greater insight into the molecular mechanisms underlying the control of vascular function by integrins. ..
- Barbero S, Mielgo A, Torres V, Teitz T, Shields D, Mikolon D, et al. Caspase-8 association with the focal adhesion complex promotes tumor cell migration and metastasis. Cancer Res. 2009;69:3755-63 pubmed publisher..This unexpected molecular collaboration provides an explanation for the continued or elevated expression of caspase-8 observed in many tumors. ..
- Mamali I, Lamprou I, Karagiannis F, Karakantza M, Lampropoulou M, Marmaras V. A beta integrin subunit regulates bacterial phagocytosis in medfly haemocytes. Dev Comp Immunol. 2009;33:858-66 pubmed publisher..Interestingly LPS is not internalized through integrins. ..
- Goody M, Henry C. Dynamic interactions between cells and their extracellular matrix mediate embryonic development. Mol Reprod Dev. 2010;77:475-88 pubmed publisher..Finally, we suggest that analysis of cell-matrix interactions at multiple levels (molecules, cells, tissues) in vivo is critical for an integrated understanding because different information can be acquired from all size scales. ..
- Kozloski G, Carraway C, Carraway K. Mechanistic and signaling analysis of Muc4-ErbB2 signaling module: new insights into the mechanism of ligand-independent ErbB2 activity. J Cell Physiol. 2010;224:649-57 pubmed publisher..Our microarray analysis indicates that Muc4 expression promotes cell migration by increasing the phosphorylation of the focal adhesion kinase and also through an increase in the levels of beta-catenin. ..
- Israeli S, Amsler K, Zheleznova N, Wilson P. Abnormalities in focal adhesion complex formation, regulation, and function in human autosomal recessive polycystic kidney disease epithelial cells. Am J Physiol Cell Physiol. 2010;298:C831-46 pubmed publisher..Paxillin coimmunoprecipitation analyses suggested that fibrocystin-1 was a component of the normal focal adhesion complex and that actin and fibrocystin-1 were lost from ARPKD complexes. ..
- Sen T, Dutta A, Chatterjee A. Epigallocatechin-3-gallate (EGCG) downregulates gelatinase-B (MMP-9) by involvement of FAK/ERK/NFkappaB and AP-1 in the human breast cancer cell line MDA-MB-231. Anticancer Drugs. 2010;21:632-44 pubmed..We propose EGCG as a potential inhibitor of the expression and activity of MMP-9 by a process involving FAK/ERK and transcription factorsin MDA-MB-231. ..
- Andersson S, D Arcy P, Larsson O, Sehat B. Focal adhesion kinase (FAK) activates and stabilizes IGF-1 receptor. Biochem Biophys Res Commun. 2009;387:36-41 pubmed publisher..Furthermore, the stability of IGF-1R was decreased upon FAK siRNA or inactivation. Taken together, our data suggest a role for FAK in phosphorylation, signaling and stability of the IGF-1R. ..
- Bateman N, Sun M, Hood B, Flint M, Conrads T. Defining central themes in breast cancer biology by differential proteomics: conserved regulation of cell spreading and focal adhesion kinase. J Proteome Res. 2010;9:5311-24 pubmed publisher..These analyses provide insights into conservation of protein expression across breast cancer cell subtypes, a subset of which warrants further investigation for their roles in the regulation of cell spreading and FAK in breast cancer. ..
- Dalyot Herman N, Delgado Lopez F, Gewirtz D, Gupton J, Schwartz E. Interference with endothelial cell function by JG-03-14, an agent that binds to the colchicine site on microtubules. Biochem Pharmacol. 2009;78:1167-77 pubmed publisher..They also provide the first report of anti-vascular activity for this class of compounds. ..
- Jin L, Hastings N, Blackman B, Somlyo A. Mechanical properties of the extracellular matrix alter expression of smooth muscle protein LPP and its partner palladin; relationship to early atherosclerosis and vascular injury. J Muscle Res Cell Motil. 2009;30:41-55 pubmed publisher..In conclusion, expression of LPP and palladin are modulated by a mix of mechanical cues, oxidative stress and substrate composition which translate into their up or down regulation in vessel wall injury and early atherogenesis. ..
- Peng L, Ran Y, Hu H, Yu L, Liu Q, Zhou Z, et al. Secreted LOXL2 is a novel therapeutic target that promotes gastric cancer metastasis via the Src/FAK pathway. Carcinogenesis. 2009;30:1660-9 pubmed publisher..Overall, our data revealed that LOXL2 overexpression, a frequent event in gastric carcinoma progression, contributes to tumor cell invasion and metastasis, and LOXL2 may be a therapeutic target for preventing and treating metastases. ..
- Atherton P, Szewczyk N, Selby A, Rankin D, Hillier K, Smith K, et al. Cyclic stretch reduces myofibrillar protein synthesis despite increases in FAK and anabolic signalling in L6 cells. J Physiol. 2009;587:3719-27 pubmed publisher..We report for the first time that acute cyclic stretch specifically suppresses MPS, despite increases in activity/phosphorylation of elements thought to increase anabolism. ..