Focal adhesion - Homo sapiens (human)
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.
Cellular Processes; Cellular community - eukaryotes
Pathway map Ortholog table
N00393 ITGA/B-RhoGAP-RhoA signaling pathway
N01068 ITGA/B-FAK-RAC signaling pathway
N01080 ITGA/B-TALIN/VINCULIN signaling pathway
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)
D10190 Tivozanib hydrochloride (USAN)
D11344 Telisotuzumab vedotin (USAN)
D11977 Fruquintinib (JAN/USAN)
D12398 Oremepermin alfa (USAN/INN)
D12635 Sozinibercept (USAN/INN)
Homo sapiens (human) [GN:
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]
2013 EMP2; epithelial membrane protein 2 [KO: K26256]
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]
2012 EMP1; epithelial membrane protein 1 [KO: K26255]
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: 220.127.116.11]
9475 ROCK2; Rho associated coiled-coil containing protein kinase 2 [KO: K17388] [EC: 18.104.22.168]
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: 22.214.171.124]
8394 PIP5K1A; phosphatidylinositol-4-phosphate 5-kinase type 1 alpha [KO: K00889] [EC: 126.96.36.199]
8395 PIP5K1B; phosphatidylinositol-4-phosphate 5-kinase type 1 beta [KO: K00889] [EC: 188.8.131.52]
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: 184.108.40.206]
5293 PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO: K00922] [EC: 220.127.116.11]
5291 PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO: K00922] [EC: 18.104.22.168]
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]
C04637 1-Phosphatidyl-D-myo-inositol 4,5-bisphosphate
Berman AE, Kozlova NI, Morozevich GE.
Integrins: structure and signaling.
Lee JW, Juliano R.
Mitogenic signal transduction by integrin- and growth factor receptor-mediated pathways.
Mol Cells 17:188-202 (2004)
Danen EH, Yamada KM.
Fibronectin, integrins, and growth control.
Guo W, Giancotti FG.
Integrin signalling during tumour progression.
Petit V, Thiery JP.
Focal adhesions: structure and dynamics.
Stupack DG, Cheresh DA.
Get a ligand, get a life: integrins, signaling and cell survival.
Focal adhesion kinase: the first ten years.
Mitra SK, Hanson DA, Schlaepfer DD.
Focal adhesion kinase: in command and control of cell motility.
Comoglio PM, Boccaccio C, Trusolino L.
Interactions between growth factor receptors and adhesion molecules: breaking the rules.
Schlaepfer DD, Mitra SK.
Multiple connections link FAK to cell motility and invasion.
Burridge K, Wennerberg K.
Rho and Rac take center stage.
Schmitz AA, Govek EE, Bottner B, Van Aelst L.
Rho GTPases: signaling, migration, and invasion.
Vanhaesebroeck B, Alessi DR.
The PI3K-PDK1 connection: more than just a road to PKB.
Nicholson KM, Anderson NG.
The protein kinase B/Akt signalling pathway in human malignancy.
Oloumi A, McPhee T, Dedhar S.
Regulation of E-cadherin expression and beta-catenin/Tcf transcriptional activity by the integrin-linked kinase.
Paxillin and focal adhesion signalling.
Hlobilkova A, Knillova J, Bartek J, Lukas J, Kolar Z.
The mechanism of action of the tumour suppressor gene PTEN.
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 147:19-25 (2003)
hsa04060 Cytokine-cytokine receptor interaction
hsa04070 Phosphatidylinositol signaling system
hsa04810 Regulation of actin cytoskeleton