| Entry |
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| Name |
Focal adhesion
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| Description |
Cell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the cell-extracellular matrix contact points, specialized structures are formed and termed focal adhesions, where bundles of actin filaments are anchored to transmembrane receptors of the integrin family through a multi-molecular complex of junctional plaque proteins. Some of the constituents of focal adhesions participate in the structural link between membrane receptors and the actin cytoskeleton, while others are signalling molecules, including different protein kinases and phosphatases, their substrates, and various adapter proteins. Integrin signaling is dependent upon the non-receptor tyrosine kinase activities of the FAK and src proteins as well as the adaptor protein functions of FAK, src and Shc to initiate downstream signaling events. These signalling events culminate in reorganization of the actin cytoskeleton; a prerequisite for changes in cell shape and motility, and gene expression. Similar morphological alterations and modulation of gene expression are initiated by the binding of growth factors to their respective receptors, emphasizing the considerable crosstalk between adhesion- and growth factor-mediated signalling.
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| Class |
Cellular Processes; Cell communication
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| Pathway map |
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| Disease |
| Glanzmann thrombasthenia | | PTEN hamartoma tumor syndrome (PHTS) | | Caveolinopathies | | Pierson syndrome | | Syndromic X-linked mental retardation with epilepsy or seizures | | Hereditary angiopathy with nephropathy, aneurysms, and muscle cramps (HANAC) | | Alport syndrome | | Benign familial hematuria | | Epidermolysis bullosa, hemidesmosomal | | Epidermolysis bullosa, junctional | | Congenital muscular dystrophies (CMD/MDC) | | Limb-girdle muscular dystrophy (LGMD) | | Myofibrillar myopathies (MFM) | | Nephrotic syndrome and focal segmental glomerulosclerosis | | Familial thoracic aortic aneurysm and dissection (TAAD) | | Ehlers-Danlos syndrome (EDS) | | Vitreoretinal degeneration | | Laryngoonychocutaneous syndrome | | Porencephaly | | Lethal congenital contractural syndrome (LCCS) | | Brain small vessel disease with Axenfeld-Rieger anomaly | | FG syndrome (FGS) | | Pilomatricoma | | VACTERL/VATER association | | Hypomagnesemia | | Juvenile-onset dystonia | | Glomerulopathy with fibronectin deposits (GFND) | | Growth delay due to insulin-like growth factor I resistance | | X-linked chronic idiopathic intestinal pseudo-obstruction |
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| Other DBs |
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| Reference |
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| Authors |
Berman AE, Kozlova NI, Morozevich GE. |
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| Title |
Integrins: structure and signaling. |
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| Journal |
Biochemistry (Mosc) 68:1284-99 (2003) |
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| Reference |
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| Authors |
Lee JW, Juliano R. |
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| Title |
Mitogenic signal transduction by integrin- and growth factor receptor-mediated pathways. |
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| Journal |
Mol Cells 17:188-202 (2004) |
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| Reference |
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| Authors |
Danen EH, Yamada KM. |
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| Title |
Fibronectin, integrins, and growth control. |
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| Journal |
J Cell Physiol 189:1-13 (2001) |
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| Reference |
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| Authors |
Guo W, Giancotti FG. |
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| Title |
Integrin signalling during tumour progression. |
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| Journal |
Nat Rev Mol Cell Biol 5:816-26 (2004) |
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| Reference |
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| Authors |
Petit V, Thiery JP. |
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| Title |
Focal adhesions: structure and dynamics. |
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| Journal |
Biol Cell 92:477-94 (2000) |
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| Reference |
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| Authors |
Stupack DG, Cheresh DA. |
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| Title |
Get a ligand, get a life: integrins, signaling and cell survival. |
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| Journal |
J Cell Sci 115:3729-38 (2002) |
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| Reference |
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| Authors |
Parsons JT. |
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| Title |
Focal adhesion kinase: the first ten years. |
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| Journal |
J Cell Sci 116:1409-16 (2003) |
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| Reference |
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| Authors |
Mitra SK, Hanson DA, Schlaepfer DD. |
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| Title |
Focal adhesion kinase: in command and control of cell motility. |
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| Journal |
Nat Rev Mol Cell Biol 6:56-68 (2005) |
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| Reference |
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| Authors |
Comoglio PM, Boccaccio C, Trusolino L. |
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| Title |
Interactions between growth factor receptors and adhesion molecules: breaking the rules. |
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| Journal |
Curr Opin Cell Biol 15:565-71 (2003) |
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| Reference |
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| Authors |
Schlaepfer DD, Mitra SK. |
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| Title |
Multiple connections link FAK to cell motility and invasion. |
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| Journal |
Curr Opin Genet Dev 14:92-101 (2004) |
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| Reference |
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| Authors |
Burridge K, Wennerberg K. |
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| Title |
Rho and Rac take center stage. |
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| Journal |
Cell 116:167-79 (2004) |
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| Reference |
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| Authors |
Schmitz AA, Govek EE, Bottner B, Van Aelst L. |
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| Title |
Rho GTPases: signaling, migration, and invasion. |
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| Journal |
Exp Cell Res 261:1-12 (2000) |
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| Reference |
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| Authors |
Vanhaesebroeck B, Alessi DR. |
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| Title |
The PI3K-PDK1 connection: more than just a road to PKB. |
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| Journal |
Biochem J 346 Pt 3:561-76 (2000) |
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| Reference |
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| Authors |
Nicholson KM, Anderson NG. |
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| Title |
The protein kinase B/Akt signalling pathway in human malignancy. |
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| Journal |
Cell Signal 14:381-95 (2002) |
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| Reference |
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| Authors |
Oloumi A, McPhee T, Dedhar S. |
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| Title |
Regulation of E-cadherin expression and beta-catenin/Tcf transcriptional activity by the integrin-linked kinase. |
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| Journal |
Biochim Biophys Acta 1691:1-15 (2004) |
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| Reference |
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| Authors |
Turner CE. |
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| Title |
Paxillin and focal adhesion signalling. |
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| Journal |
Nat Cell Biol 2:E231-6 (2000) |
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| Reference |
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| Authors |
Hlobilkova A, Knillova J, Bartek J, Lukas J, Kolar Z. |
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| Title |
The mechanism of action of the tumour suppressor gene PTEN. |
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| Journal |
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 147:19-25 (2003) |
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| KO pathway |
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