Entry
Name
Focal adhesion
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.
Class
Cellular Processes; Cellular community - eukaryotes
BRITE hierarchy
Pathway map
Ortholog table
Other DBs
Orthology
K06250 secreted phosphoprotein 1
K06253 integrin binding sialoprotein
K26256 epithelial membrane protein 2
K04359 platelet-derived growth factor subunit A
K17386 platelet-derived growth factor subunit B
K05450 platelet derived growth factor C/D
K04357 epidermal growth factor
K05459 insulin-like growth factor 1
K05448 vascular endothelial growth factor A
K16858 vascular endothelial growth factor B
K05449 vascular endothelial growth factor C/D
K05460 hepatocyte growth factor
K26255 epithelial membrane protein 1
K05732 glucocorticoid receptor DNA-binding factor 1
K13709 Rho GTPase-activating protein 5
K04513 Ras homolog gene family, member A
K10351 myosin regulatory light chain 2
K12753 myosin regulatory light chain 5
K12754 myosin regulatory light chain 7
K12755 myosin regulatory light chain 9
K12756 myosin regulatory light chain 10
K12757 myosin regulatory light chain 12
K12758 fast skeletal myosin light chain 2
K06269 serine/threonine-protein phosphatase PP1 catalytic subunit [EC:3.1.3.16 ]
K06270 protein phosphatase 1 regulatory subunit 12A
K12329 protein phosphatase 1 regulatory subunit 12B
K17457 protein phosphatase 1 regulatory subunit 12C
K04349 Ras-specific guanine nucleotide-releasing factor 1
K06274 vasodilator-stimulated phosphoprotein
K00922 phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153 ]
K02649 phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K05730 guanine nucleotide exchange factor VAV
K04392 Ras-related C3 botulinum toxin substrate 1
K07860 Ras-related C3 botulinum toxin substrate 2
K07861 Ras-related C3 botulinum toxin substrate 3
K04393 cell division control protein 42
K05726 breast cancer anti-estrogen resistance 1
K04438 C-crk adapter molecule crk
K13708 dedicator of cytokinesis protein 1
K06277 Rap guanine nucleotide exchange factor 1
K04353 Ras-related protein Rap-1A
K07836 Ras-related protein Rap-1B
K04440 mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24 ]
K04448 transcription factor AP-1
K04365 B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K06279 SHC-transforming protein 1
K17447 SHC-transforming protein 2
K17448 SHC-transforming protein 3
K17449 SHC-transforming protein 4
K04364 growth factor receptor-bound protein 2
K04366 RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04375 ETS domain-containing protein Elk-1
K04503 G1/S-specific cyclin-D1
K10151 G1/S-specific cyclin-D2
K10152 G1/S-specific cyclin-D3
K16060 baculoviral IAP repeat-containing protein 2/3
K02158 Bcl-2-antagonist of cell death
K02161 apoptosis regulator Bcl-2
Compound
C04637 1-Phosphatidyl-D-myo-inositol 4,5-bisphosphate
C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference
Authors
Berman AE, Kozlova NI, Morozevich GE.
Title
Integrins: structure and signaling.
Journal
Reference
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
Authors
Danen EH, Yamada KM.
Title
Fibronectin, integrins, and growth control.
Journal
Reference
Authors
Guo W, Giancotti FG.
Title
Integrin signalling during tumour progression.
Journal
Reference
Authors
Petit V, Thiery JP.
Title
Focal adhesions: structure and dynamics.
Journal
Reference
Authors
Stupack DG, Cheresh DA.
Title
Get a ligand, get a life: integrins, signaling and cell survival.
Journal
Reference
Authors
Parsons JT.
Title
Focal adhesion kinase: the first ten years.
Journal
Reference
Authors
Mitra SK, Hanson DA, Schlaepfer DD.
Title
Focal adhesion kinase: in command and control of cell motility.
Journal
Reference
Authors
Comoglio PM, Boccaccio C, Trusolino L.
Title
Interactions between growth factor receptors and adhesion molecules: breaking the rules.
Journal
Reference
Authors
Schlaepfer DD, Mitra SK.
Title
Multiple connections link FAK to cell motility and invasion.
Journal
Reference
Authors
Burridge K, Wennerberg K.
Title
Rho and Rac take center stage.
Journal
Reference
Authors
Schmitz AA, Govek EE, Bottner B, Van Aelst L.
Title
Rho GTPases: signaling, migration, and invasion.
Journal
Reference
Authors
Vanhaesebroeck B, Alessi DR.
Title
The PI3K-PDK1 connection: more than just a road to PKB.
Journal
Reference
Authors
Nicholson KM, Anderson NG.
Title
The protein kinase B/Akt signalling pathway in human malignancy.
Journal
Reference
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
Reference
Authors
Turner CE.
Title
Paxillin and focal adhesion signalling.
Journal
Reference
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
ko04060 Cytokine-cytokine receptor interaction
ko04070 Phosphatidylinositol signaling system
ko04810 Regulation of actin cytoskeleton
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