Entry |
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Name |
Focal adhesion - Homo sapiens (human)
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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; Cellular community - eukaryotes
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Pathway map |

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Network |
nt06135 Cytoskeletal regulation (viruses and bacteria) nt06167 Human cytomegalovirus (HCMV) |
Element |
N00393 | ITGA/B-RhoGAP-RhoA signaling pathway |
N01068 | ITGA/B-FAK-RAC signaling pathway |
N01080 | ITGA/B-TALIN/VINCULIN signaling pathway |
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Disease |
H00801 | Familial thoracic aortic aneurysm and dissection |
H00805 | Vitreoretinal degeneration |
H00813 | Laryngo onycho cutaneous syndrome |
H00877 | Brain small vessel disease |
H01195 | VACTERL/VATER association |
H01255 | Juvenile-onset dystonia |
H01276 | Chronic idiopathic intestinal pseudo-obstruction |
H01526 | Legg-Calve-Perthes Disease |
H02064 | Atelosteogenesis type I and III |
H02066 | Achondrogenesis type II |
H02241 | Ehlers-Danlos syndrome cardiac valvular type |
H02243 | Ehlers-Danlos syndrome arthrochalasia type |
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Drug |
D04660 | Lamifiban hydrochloride (USAN) |
D09342 | Etaracizumab (USAN/INN) |
D09929 | Maraciclatide (USAN/INN) |
D09945 | Pegdinetanib (USAN/INN) |
D10028 | Valategrast hydrochloride (USAN) |
D10173 | Tivantinib (JAN/USAN/INN) |
D11344 | Telisotuzumab vedotin (USAN) |
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Other DBs |
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Organism |
Homo sapiens (human) [GN: hsa]
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Gene |
1277 | COL1A1; collagen type I alpha 1 chain [KO:K06236] |
1278 | COL1A2; collagen type I alpha 2 chain [KO:K06236] |
1280 | COL2A1; collagen type II alpha 1 chain [KO:K19719] |
1284 | COL4A2; collagen type IV alpha 2 chain [KO:K06237] |
1286 | COL4A4; collagen type IV alpha 4 chain [KO:K06237] |
1288 | COL4A6; collagen type IV alpha 6 chain [KO:K06237] |
1282 | COL4A1; collagen type IV alpha 1 chain [KO:K06237] |
1287 | COL4A5; collagen type IV alpha 5 chain [KO:K06237] |
1285 | COL4A3; collagen type IV alpha 3 chain [KO:K06237] |
1291 | COL6A1; collagen type VI alpha 1 chain [KO:K06238] |
1292 | COL6A2; collagen type VI alpha 2 chain [KO:K06238] |
1293 | COL6A3; collagen type VI alpha 3 chain [KO:K06238] |
1297 | COL9A1; collagen type IX alpha 1 chain [KO:K08131] |
1298 | COL9A2; collagen type IX alpha 2 chain [KO:K08131] |
1299 | COL9A3; collagen type IX alpha 3 chain [KO:K08131] |
1311 | COMP; cartilage oligomeric matrix protein [KO:K04659] |
3381 | IBSP; integrin binding sialoprotein [KO:K06253] |
3674 | ITGA2B; integrin subunit alpha 2b [KO:K06476] |
8515 | ITGA10; integrin subunit alpha 10 [KO:K06586] |
5154 | PDGFA; platelet derived growth factor subunit A [KO:K04359] |
5155 | PDGFB; platelet derived growth factor subunit B [KO:K17386] |
56034 | PDGFC; platelet derived growth factor C [KO:K05450] |
80310 | PDGFD; platelet derived growth factor D [KO:K05450] |
3479 | IGF1; insulin like growth factor 1 [KO:K05459] |
7422 | VEGFA; vascular endothelial growth factor A [KO:K05448] |
7423 | VEGFB; vascular endothelial growth factor B [KO:K16858] |
7424 | VEGFC; vascular endothelial growth factor C [KO:K05449] |
2277 | VEGFD; vascular endothelial growth factor D [KO:K05449] |
2909 | ARHGAP35; Rho GTPase activating protein 35 [KO:K05732] |
394 | ARHGAP5; Rho GTPase activating protein 5 [KO:K13709] |
387 | RHOA; ras homolog family member A [KO:K04513] |
1729 | DIAPH1; diaphanous related formin 1 [KO:K05740] |
6093 | ROCK1; Rho associated coiled-coil containing protein kinase 1 [KO:K04514] [EC:2.7.11.1] |
9475 | ROCK2; Rho associated coiled-coil containing protein kinase 2 [KO:K17388] [EC:2.7.11.1] |
29895 | MYLPF; myosin light chain, phosphorylatable, fast skeletal muscle [KO:K12758] |
4659 | PPP1R12A; protein phosphatase 1 regulatory subunit 12A [KO:K06270] |
4660 | PPP1R12B; protein phosphatase 1 regulatory subunit 12B [KO:K12329] |
54776 | PPP1R12C; protein phosphatase 1 regulatory subunit 12C [KO:K17457] |
23396 | PIP5K1C; phosphatidylinositol-4-phosphate 5-kinase type 1 gamma [KO:K00889] [EC:2.7.1.68] |
8394 | PIP5K1A; phosphatidylinositol-4-phosphate 5-kinase type 1 alpha [KO:K00889] [EC:2.7.1.68] |
8395 | PIP5K1B; phosphatidylinositol-4-phosphate 5-kinase type 1 beta [KO:K00889] [EC:2.7.1.68] |
5923 | RASGRF1; Ras protein specific guanine nucleotide releasing factor 1 [KO:K04349] |
7408 | VASP; vasodilator stimulated phosphoprotein [KO:K06274] |
5290 | PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153] |
5293 | PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153] |
5291 | PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153] |
5295 | PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649] |
5296 | PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649] |
8503 | PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649] |
10451 | VAV3; vav guanine nucleotide exchange factor 3 [KO:K05730] |
7409 | VAV1; vav guanine nucleotide exchange factor 1 [KO:K05730] |
7410 | VAV2; vav guanine nucleotide exchange factor 2 [KO:K05730] |
998 | CDC42; cell division cycle 42 [KO:K04393] |
9564 | BCAR1; BCAR1 scaffold protein, Cas family member [KO:K05726] |
1398 | CRK; CRK proto-oncogene, adaptor protein [KO:K04438] |
1399 | CRKL; CRK like proto-oncogene, adaptor protein [KO:K04438] |
1793 | DOCK1; dedicator of cytokinesis 1 [KO:K13708] |
2889 | RAPGEF1; Rap guanine nucleotide exchange factor 1 [KO:K06277] |
5906 | RAP1A; RAP1A, member of RAS oncogene family [KO:K04353] |
5908 | RAP1B; RAP1B, member of RAS oncogene family [KO:K07836] |
3725 | JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448] |
2885 | GRB2; growth factor receptor bound protein 2 [KO:K04364] |
6654 | SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099] |
6655 | SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099] |
3265 | HRAS; HRas proto-oncogene, GTPase [KO:K02833] |
2002 | ELK1; ETS transcription factor ELK1 [KO:K04375] |
329 | BIRC2; baculoviral IAP repeat containing 2 [KO:K16060] |
330 | BIRC3; baculoviral IAP repeat containing 3 [KO:K16060] |
572 | BAD; BCL2 associated agonist of cell death [KO:K02158] |
596 | BCL2; BCL2 apoptosis regulator [KO:K02161] |
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Compound |
C04637 | 1-Phosphatidyl-D-myo-inositol 4,5-bisphosphate |
C05981 | Phosphatidylinositol-3,4,5-trisphosphate |
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Reference |
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Authors |
Berman AE, Kozlova NI, Morozevich GE. |
Title |
Integrins: structure and signaling. |
Journal |
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Reference |
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Authors |
Lee JW, Juliano R. |
Title |
Mitogenic signal transduction by integrin- and growth factor receptor-mediated pathways. |
Journal |
Mol Cells 17:188-202 (2004) |
Reference |
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Authors |
Danen EH, Yamada KM. |
Title |
Fibronectin, integrins, and growth control. |
Journal |
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Reference |
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Authors |
Guo W, Giancotti FG. |
Title |
Integrin signalling during tumour progression. |
Journal |
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Reference |
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Authors |
Petit V, Thiery JP. |
Title |
Focal adhesions: structure and dynamics. |
Journal |
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Reference |
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Authors |
Stupack DG, Cheresh DA. |
Title |
Get a ligand, get a life: integrins, signaling and cell survival. |
Journal |
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Reference |
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Authors |
Parsons JT. |
Title |
Focal adhesion kinase: the first ten years. |
Journal |
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Reference |
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Authors |
Mitra SK, Hanson DA, Schlaepfer DD. |
Title |
Focal adhesion kinase: in command and control of cell motility. |
Journal |
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Reference |
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Authors |
Comoglio PM, Boccaccio C, Trusolino L. |
Title |
Interactions between growth factor receptors and adhesion molecules: breaking the rules. |
Journal |
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Reference |
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Authors |
Schlaepfer DD, Mitra SK. |
Title |
Multiple connections link FAK to cell motility and invasion. |
Journal |
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Reference |
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Authors |
Burridge K, Wennerberg K. |
Title |
Rho and Rac take center stage. |
Journal |
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Reference |
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Authors |
Schmitz AA, Govek EE, Bottner B, Van Aelst L. |
Title |
Rho GTPases: signaling, migration, and invasion. |
Journal |
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Reference |
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Authors |
Vanhaesebroeck B, Alessi DR. |
Title |
The PI3K-PDK1 connection: more than just a road to PKB. |
Journal |
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Reference |
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Authors |
Nicholson KM, Anderson NG. |
Title |
The protein kinase B/Akt signalling pathway in human malignancy. |
Journal |
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Reference |
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Authors |
Oloumi A, McPhee T, Dedhar S. |
Title |
Regulation of E-cadherin expression and beta-catenin/Tcf transcriptional activity by the integrin-linked kinase. |
Journal |
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Reference |
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Authors |
Turner CE. |
Title |
Paxillin and focal adhesion signalling. |
Journal |
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Reference |
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Authors |
Hlobilkova A, Knillova J, Bartek J, Lukas J, Kolar Z. |
Title |
The mechanism of action of the tumour suppressor gene PTEN. |
Journal |
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 147:19-25 (2003) |
Related pathway |
hsa04060 | Cytokine-cytokine receptor interaction |
hsa04070 | Phosphatidylinositol signaling system |
hsa04810 | Regulation of actin cytoskeleton |
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KO pathway |
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