KEGG   PATHWAY: ko04510Help
Entry
ko04510                     Pathway                                

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; Cell communication
BRITE hierarchy
Pathway map
Focal adhesion
ko04510

All organismsOrtholog table
Disease
H00226  
Glanzmann thrombasthenia
H00539  
PTEN hamartoma tumor syndrome (PHTS)
H00567  
Caveolinopathies
H00576  
Pierson syndrome
H00577  
Syndromic X-linked mental retardation with epilepsy or seizures
H00579  
Hereditary angiopathy with nephropathy, aneurysms, and muscle cramps (HANAC)
H00581  
Alport syndrome
H00582  
Benign familial hematuria
H00585  
Epidermolysis bullosa, hemidesmosomal
H00586  
Epidermolysis bullosa, junctional
H00590  
Congenital muscular dystrophies (CMD/MDC)
H00593  
Limb-girdle muscular dystrophy (LGMD)
H00595  
Myofibrillar myopathies (MFM)
H00626  
Nephrotic syndrome and focal segmental glomerulosclerosis
H00801  
Familial thoracic aortic aneurysm and dissection (TAAD)
H00802  
Ehlers-Danlos syndrome (EDS)
H00805  
Vitreoretinal degeneration
H00813  
Laryngo onycho cutaneous syndrome
H00839  
Porencephaly
H00865  
Lethal congenital contractural syndrome (LCCS)
H00877  
Brain small vessel disease with Axenfeld-Rieger anomaly
H00894  
FG syndrome (FGS)
H00947  
Pilomatricoma
H01195  
VACTERL/VATER association
H01210  
Hypomagnesemia
H01255  
Juvenile-onset dystonia
H01260  
Glomerulopathy with fibronectin deposits (GFND)
H01274  
Growth delay due to insulin-like growth factor I resistance
H01276  
X-linked chronic idiopathic intestinal pseudo-obstruction
H01338  
Myosclerosis
H01340  
Bethlem myopathy
H01341  
Collagen VI myopathy
Other DBs
BSID: 
GO: 
Orthology
K06236  
collagen, type I/II/III/V/XI/XXIV/XXVII, alpha
K06237  
collagen, type IV, alpha
K06238  
collagen, type VI, alpha
K05637  
laminin, alpha 1/2
K06240  
laminin, alpha 3/5
K06241  
laminin, alpha 4
K05636  
laminin, beta 1
K06243  
laminin, beta 2
K06244  
laminin, beta 3
K06245  
laminin, beta 4
K05635  
laminin, gamma 1
K06246  
laminin, gamma 2
K06247  
laminin, gamma 3
K06248  
chondroadherin
K06249  
reelin [EC:3.4.21.-]
K16857  
thrombospondin 1
K04659  
thrombospondin 2/3/4/5
K05717  
fibronectin 1
K06250  
secreted phosphoprotein 1
K06251  
vitronectin
K06252  
tenascin
K03900  
von Willebrand factor
K06253  
integrin binding sialoprotein
K06480  
integrin alpha 1
K06481  
integrin alpha 2
K06476  
integrin alpha 2B
K06482  
integrin alpha 3
K06483  
integrin alpha 4
K06484  
integrin alpha 5
K06485  
integrin alpha 6
K06583  
integrin alpha 7
K06584  
integrin alpha 8
K06585  
integrin alpha 9
K06586  
integrin alpha 10
K06587  
integrin alpha 11
K06487  
integrin alpha V
K05719  
integrin beta 1
K06493  
integrin beta 3
K06525  
integrin beta 4
K06588  
integrin beta 5
K06589  
integrin beta 6
K06590  
integrin beta 7
K06591  
integrin beta 8
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
K16859  
placenta growth factor
K05449  
vascular endothelial growth factor C/D
K05460  
hepatocyte growth factor
K04363  
platelet-derived growth factor receptor alpha [EC:2.7.10.1]
K05089  
platelet-derived growth factor receptor beta [EC:2.7.10.1]
K05087  
insulin-like growth factor 1 receptor [EC:2.7.10.1]
K05098  
kinase insert domain protein receptor [EC:2.7.10.1]
K04361  
epidermal growth factor receptor [EC:2.7.10.1]
K05096  
FMS-like tyrosine kinase 1 [EC:2.7.10.1]
K05097  
FMS-like tyrosine kinase 4 [EC:2.7.10.1]
K05099  
proto-oncogene tyrosine-protein kinase Met [EC:2.7.10.1]
K05083  
receptor tyrosine-protein kinase erbB-2 [EC:2.7.10.1]
K05704  
tyrosine-protein kinase Src [EC:2.7.10.2]
K05732  
glucocorticoid receptor DNA-binding factor 1
K13709  
Rho GTPase-activating protein 5
K04513  
Ras homolog gene family, member A
K05740  
diaphanous 1
K04514  
Rho-associated protein kinase 1 [EC:2.7.11.1]
K17388  
Rho-associated protein kinase 2 [EC:2.7.11.1]
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
K00907  
myosin-light-chain kinase [EC:2.7.11.18]
K05692  
actin beta/gamma 1
K04349  
Ras-specific guanine nucleotide-releasing factor 1
K03853  
calpain-2 [EC:3.4.22.53]
K05699  
actinin alpha
K06271  
talin
K04437  
filamin
K05760  
paxillin
K06272  
integrin-linked kinase [EC:2.7.11.1]
K06273  
zyxin
K06274  
vasodilator-stimulated phosphoprotein
K05700  
vinculin
K06275  
parvin
K06276  
3-phosphoinositide dependent protein kinase-1 [EC:2.7.11.1]
K04456  
RAC serine/threonine-protein kinase [EC:2.7.11.1]
K03083  
glycogen synthase kinase 3 beta [EC:2.7.11.26]
K02105  
catenin beta 1
K02677  
classical protein kinase C [EC:2.7.11.13]
K05725  
focal adhesion kinase 1 [EC:2.7.10.2]
K00922  
phosphatidylinositol-4,5-bisphosphate 3-kinase [EC:2.7.1.153]
K02649  
phosphoinositide-3-kinase, regulatory subunit
K01110  
phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [EC:3.1.3.67 3.1.3.48 3.1.3.16]
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
K04409  
p21-activated kinase 1 [EC:2.7.11.1]
K04410  
p21-activated kinase 2 [EC:2.7.11.1]
K05733  
p21-activated kinase 3 [EC:2.7.11.1]
K05734  
p21-activated kinase 4 [EC:2.7.11.1]
K05735  
p21-activated kinase 6 [EC:2.7.11.1]
K05736  
p21-activated kinase 7 [EC:2.7.11.1]
K04393  
cell division control protein 42
K05726  
breast cancer anti-estrogen resistance 1
K04438  
proto-oncogene C-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  
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]
K06278  
caveolin 1
K12958  
caveolin 2
K12959  
caveolin 3
K05703  
tyrosine-protein kinase Fyn [EC:2.7.10.2]
K06279  
SHC- transforming protein 1
K17447  
SHC- transforming protein 2
K17448  
SHC- transforming protein 3
K17449  
SHC- transforming protein 4
K04364  
growth factor receptor-binding protein 2
K03099  
son of sevenless
K02833  
GTPase HRas
K04366  
RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04368  
mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04371  
mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04375  
ETS domain-containing protein Elk-1
K04503  
cyclin D1
K10151  
cyclin D2
K10152  
cyclin D3
K16060  
baculoviral IAP repeat-containing protein 2/3
K04725  
E3 ubiquitin-protein ligase XIAP
K02158  
BCL2-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
Biochemistry (Mosc) 68:1284-99 (2003)
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
J Cell Physiol 189:1-13 (2001)
Reference
  Authors
Guo W, Giancotti FG.
  Title
Integrin signalling during tumour progression.
  Journal
Nat Rev Mol Cell Biol 5:816-26 (2004)
Reference
  Authors
Petit V, Thiery JP.
  Title
Focal adhesions: structure and dynamics.
  Journal
Biol Cell 92:477-94 (2000)
Reference
  Authors
Stupack DG, Cheresh DA.
  Title
Get a ligand, get a life: integrins, signaling and cell survival.
  Journal
J Cell Sci 115:3729-38 (2002)
Reference
  Authors
Parsons JT.
  Title
Focal adhesion kinase: the first ten years.
  Journal
J Cell Sci 116:1409-16 (2003)
Reference
  Authors
Mitra SK, Hanson DA, Schlaepfer DD.
  Title
Focal adhesion kinase: in command and control of cell motility.
  Journal
Nat Rev Mol Cell Biol 6:56-68 (2005)
Reference
  Authors
Comoglio PM, Boccaccio C, Trusolino L.
  Title
Interactions between growth factor receptors and adhesion molecules: breaking the rules.
  Journal
Curr Opin Cell Biol 15:565-71 (2003)
Reference
  Authors
Schlaepfer DD, Mitra SK.
  Title
Multiple connections link FAK to cell motility and invasion.
  Journal
Curr Opin Genet Dev 14:92-101 (2004)
Reference
  Authors
Burridge K, Wennerberg K.
  Title
Rho and Rac take center stage.
  Journal
Cell 116:167-79 (2004)
Reference
  Authors
Schmitz AA, Govek EE, Bottner B, Van Aelst L.
  Title
Rho GTPases: signaling, migration, and invasion.
  Journal
Exp Cell Res 261:1-12 (2000)
Reference
  Authors
Vanhaesebroeck B, Alessi DR.
  Title
The PI3K-PDK1 connection: more than just a road to PKB.
  Journal
Biochem J 346 Pt 3:561-76 (2000)
Reference
  Authors
Nicholson KM, Anderson NG.
  Title
The protein kinase B/Akt signalling pathway in human malignancy.
  Journal
Cell Signal 14:381-95 (2002)
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
Biochim Biophys Acta 1691:1-15 (2004)
Reference
  Authors
Turner CE.
  Title
Paxillin and focal adhesion signalling.
  Journal
Nat Cell Biol 2:E231-6 (2000)
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)

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