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
09140 Cellular Processes; 09144 Cellular community - eukaryotes
BRITE hierarchy
Pathway map
ko04510  Focal adhesion
ko04510

Ortholog table
Disease
H00226  Glanzmann thrombasthenia
H00520  Type II collagenopathies
H00567  Caveolinopathies
H00576  Pierson syndrome
H00579  Hereditary angiopathy with nephropathy, aneurysms, and muscle cramps (HANAC)
H00581  Alport syndrome
H00582  Benign familial hematuria
H00586  Epidermolysis bullosa, junctional
H00590  Congenital muscular dystrophies (CMD/MDC)
H00593  Limb-girdle muscular dystrophy (LGMD)
H00595  Myofibrillar myopathies (MFM)
H00801  Familial thoracic aortic aneurysm and dissection (TAAD)
H00802  Ehlers-Danlos syndrome (EDS)
H00805  Vitreoretinal degeneration
H00813  Laryngo onycho cutaneous syndrome
H00839  Porencephaly
H00877  Brain small vessel disease with hemorrhage
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  Chronic idiopathic intestinal pseudo-obstruction
H01338  Myosclerosis
H01340  Bethlem myopathy
H01341  Collagen VI myopathy
H01526  Legg-Calve-Perthes Disease
H01740  Macrothrombocytopenia
H01778  Ullrich disease
H02048  Larsen syndrome
H02064  Atelosteogenesis type I and III
H02066  Achondrogenesis type II
H02067  Boomerang dysplasia
H02070  Kniest dysplasia
H02071  Czech dysplasia
H02072  Stickler syndrome
Other DBs
BSID: 478
GO: 0005925
Orthology
K06236  collagen, type I, alpha
K19719  collagen, type II, alpha
K06237  collagen, type IV, alpha
K06238  collagen, type VI, alpha
K08131  collagen, type IX, 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 1/4
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 alpha type [EC:2.7.11.13]
K19662  classical protein kinase C beta type [EC:2.7.11.13]
K19663  classical protein kinase C gamma type [EC:2.7.11.13]
K05725  focal adhesion kinase 1 [EC:2.7.10.2]
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
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]
K05736  p21-activated kinase 5 [EC:2.7.11.1]
K05735  p21-activated kinase 6 [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  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]
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  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
K04725  E3 ubiquitin-protein ligase XIAP [EC:2.3.2.27]
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
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)
DOI:10.1002/jcp.1137
Reference
  Authors
Guo W, Giancotti FG.
  Title
Integrin signalling during tumour progression.
  Journal
Nat Rev Mol Cell Biol 5:816-26 (2004)
DOI:10.1038/nrm1490
Reference
  Authors
Petit V, Thiery JP.
  Title
Focal adhesions: structure and dynamics.
  Journal
Biol Cell 92:477-94 (2000)
DOI:10.1016/S0248-4900(00)01101-1
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)
DOI:10.1242/jcs.00071
Reference
  Authors
Parsons JT.
  Title
Focal adhesion kinase: the first ten years.
  Journal
J Cell Sci 116:1409-16 (2003)
DOI:10.1242/jcs.00373
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)
DOI:10.1038/nrm1549
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)
DOI:10.1016/S0955-0674(03)00096-6
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)
DOI:10.1016/j.gde.2003.12.002
Reference
  Authors
Burridge K, Wennerberg K.
  Title
Rho and Rac take center stage.
  Journal
Cell 116:167-79 (2004)
DOI:10.1016/S0092-8674(04)00003-0
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)
DOI:10.1006/excr.2000.5049
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)
DOI:10.1042/bj3460561
Reference
  Authors
Nicholson KM, Anderson NG.
  Title
The protein kinase B/Akt signalling pathway in human malignancy.
  Journal
Cell Signal 14:381-95 (2002)
DOI:10.1016/S0898-6568(01)00271-6
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)
DOI:10.1016/j.bbamcr.2003.12.002
Reference
  Authors
Turner CE.
  Title
Paxillin and focal adhesion signalling.
  Journal
Nat Cell Biol 2:E231-6 (2000)
DOI:10.1038/35046659
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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