KEGG   PATHWAY: esp04510
Entry
esp04510                    Pathway                                
Name
Focal adhesion - Etheostoma spectabile (orangethroat darter)
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
Pathway map
esp04510  Focal adhesion
esp04510

Other DBs
GO: 0005925
Organism
Etheostoma spectabile (orangethroat darter) [GN:esp]
Gene
116669489  col4a5; collagen alpha-5(IV) chain isoform X1 [KO:K06237]
116669655  [KO:K05703] [EC:2.7.10.2]
116669662  [KO:K06269] [EC:3.1.3.16]
116669702  sos2; son of sevenless homolog 2 isoform X1 [KO:K03099]
116669838  itgb6; integrin beta-6 [KO:K06589]
116669984  lama5; laminin subunit alpha-5 isoform X1 [KO:K06240]
116670002  pak6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
116670013  [KO:K04410] [EC:2.7.11.1]
116670120  akt1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
116670144  thbs1; thrombospondin-1 [KO:K16857]
116670486  [KO:K16859]
116670542  [KO:K05699]
116670566  prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
116670634  rock2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.1]
116670728  [KO:K06493]
116670903  chad; chondroadherin [KO:K06248]
116670942  rac1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
116670996  dock1; dedicator of cytokinesis protein 1 isoform X1 [KO:K13708]
116671118  itgb4; integrin beta-4 isoform X1 [KO:K06525]
116671146  [KO:K04659]
116671152  itga3; integrin alpha-3 [KO:K06482]
116671183  [KO:K05700]
116671215  [KO:K06236]
116671269  erbb2; receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
116671320  [KO:K06269] [EC:3.1.3.16]
116671334  [KO:K12758]
116671370  pdpk1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
116671424  ilk; integrin-linked protein kinase [KO:K06272] [EC:2.7.11.1]
116671539  [KO:K04440] [EC:2.7.11.24]
116671546  [KO:K07861]
116671707  [KO:K00907] [EC:2.7.11.18]
116672012  vegfd; vascular endothelial growth factor D [KO:K05449]
116672030  itgb1; integrin beta-1 isoform X1 [KO:K05719]
116672078  vav3; guanine nucleotide exchange factor VAV3 isoform X1 [KO:K05730]
116672459  [KO:K12757]
116672533  flt1; vascular endothelial growth factor receptor 1 [KO:K05096] [EC:2.7.10.1]
116673142  [KO:K04456] [EC:2.7.11.1]
116673147  [KO:K06274]
116673193  braf; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
116673226  [KO:K05460]
116673298  ccnd2; G1/S-specific cyclin-D2 [KO:K10151]
116673322  ppp1r12a; protein phosphatase 1 regulatory subunit 12A isoform X1 [KO:K06270]
116673333  [KO:K05636]
116673342  [KO:K04456] [EC:2.7.11.1]
116673369  igf1; insulin-like growth factor I [KO:K05459]
116673735  [KO:K05449]
116674771  crk; adapter molecule crk [KO:K04438]
116675754  pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
116675778  actn4; alpha-actinin-4 isoform X1 [KO:K05699]
116677569  [KO:K06245]
116677570  [KO:K05636]
116677748  [KO:K04448]
116678381  [KO:K00922] [EC:2.7.1.153]
116678507  arhgap35; rho GTPase-activating protein 35 [KO:K05732]
116678819  [KO:K03099]
116679334  [KO:K06238]
116679543  [KO:K04375]
116679804  [KO:K06269] [EC:3.1.3.16]
116679832  [KO:K05703] [EC:2.7.10.2]
116679987  vasp; vasodilator-stimulated phosphoprotein isoform X1 [KO:K06274]
116683329  pdgfd; platelet-derived growth factor D isoform X1 [KO:K05450]
116684671  [KO:K06237]
116685041  [KO:K04409] [EC:2.7.11.1]
116686302  arhgap5; LOW QUALITY PROTEIN: rho GTPase-activating protein 5 [KO:K13709]
116686659  ppp1cc; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
116686662  [KO:K10351]
116686712  [KO:K06275]
116686972  pak4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
116687137  vtn; vitronectin [KO:K06251]
116687400  [KO:K10351]
116687421  itga7; integrin alpha-7 isoform X1 [KO:K06583]
116687553  itga5; integrin alpha-5 [KO:K06484]
116687594  [KO:K05704] [EC:2.7.10.2]
116687691  [KO:K10152]
116687703  [KO:K04513]
116688064  [KO:K12755]
116688249  [KO:K12958]
116688259  [KO:K04513]
116688288  [KO:K04393]
116688344  [KO:K04353]
116688419  [KO:K12958]
116688422  cav3; LOW QUALITY PROTEIN: caveolin-3 [KO:K12959]
116688445  [KO:K19719]
116688517  lamb3; laminin subunit beta-3 isoform X1 [KO:K06244]
116689235  [KO:K04659]
116689248  [KO:K00889] [EC:2.7.1.68]
116689277  [KO:K06252]
116689305  [KO:K06269] [EC:3.1.3.16]
116689310  [KO:K10351]
116689477  itga2; LOW QUALITY PROTEIN: integrin alpha-2 [KO:K06481]
116689632  myl7; myosin regulatory light chain 2, atrial isoform isoform X1 [KO:K12754]
116689863  itgb5; integrin beta-5 [KO:K06588]
116689915  [KO:K02649]
116689954  [KO:K05692]
116690322  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
116690346  [KO:K05760]
116690550  [KO:K04349]
116690676  itga11; integrin alpha-11 isoform X1 [KO:K06587]
116690803  itga10; integrin alpha-10 [KO:K06586]
116691005  [KO:K06252]
116691232  zyx; zyxin [KO:K06273]
116691327  [KO:K04393]
116691343  ctnnb1; catenin beta-1 isoform X1 [KO:K02105]
116691362  [KO:K19663] [EC:2.7.11.13]
116691384  [KO:K00889] [EC:2.7.1.68]
116691433  [KO:K05725] [EC:2.7.10.2]
116691646  itga8; integrin alpha-8 [KO:K06584]
116691703  shc1; LOW QUALITY PROTEIN: SHC-transforming protein 1 [KO:K06279]
116691856  [KO:K06271]
116691873  lamb2; LOW QUALITY PROTEIN: laminin subunit beta-2 [KO:K06243]
116691899  [KO:K12958]
116691938  [KO:K05459]
116691940  [KO:K04513]
116692018  [KO:K04513]
116692048  [KO:K19719]
116692093  [KO:K04353]
116692170  [KO:K04393]
116692455  [KO:K04513]
116692515  col9a3; collagen alpha-3(IX) chain [KO:K08131]
116692529  pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116692732  [KO:K05704] [EC:2.7.10.2]
116692975  [KO:K06243]
116693071  raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
116693125  [KO:K06484]
116693200  [KO:K04437]
116693711  met; hepatocyte growth factor receptor [KO:K05099] [EC:2.7.10.1]
116693796  cav1; caveolin-1 [KO:K06278]
116693808  cav2; caveolin-2 [KO:K12958]
116693910  tln2; talin-2 isoform X1 [KO:K06271]
116694009  [KO:K05087] [EC:2.7.10.1]
116694165  [KO:K17457]
116694167  vwf; von Willebrand factor [KO:K03900]
116694204  reln; reelin isoform X1 [KO:K06249] [EC:3.4.21.-]
116694238  [KO:K04349]
116694245  hras; GTPase HRas [KO:K02833]
116694578  [KO:K04503]
116694598  bcar1; LOW QUALITY PROTEIN: breast cancer anti-estrogen resistance protein 1 [KO:K05726]
116694635  parvb; beta-parvin isoform X1 [KO:K06275]
116694636  parvg; gamma-parvin isoform X1 [KO:K06275]
116694654  [KO:K05087] [EC:2.7.10.1]
116694689  hgf; hepatocyte growth factor isoform X1 [KO:K05460]
116694773  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
116695201  [KO:K04448]
116695417  [KO:K00922] [EC:2.7.1.153]
116695430  [KO:K02649]
116695568  mylk4; myosin light chain kinase family member 4 isoform X1 [KO:K00907] [EC:2.7.11.18]
116695589  pdgfra; platelet-derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
116695590  kdr; vascular endothelial growth factor receptor 2 isoform X1 [KO:K05098] [EC:2.7.10.1]
116695614  pak2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
116696012  [KO:K04659]
116696108  pip5k1c; phosphatidylinositol 4-phosphate 5-kinase type-1 gamma isoform X1 [KO:K00889] [EC:2.7.1.68]
116696146  [KO:K02649]
116696202  [KO:K17447]
116696510  egf; pro-epidermal growth factor [KO:K04357]
116696522  pdgfc; platelet-derived growth factor C isoform X1 [KO:K05450]
116696884  pdgfrb; platelet-derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
116697085  lamc2; LOW QUALITY PROTEIN: laminin subunit gamma-2 [KO:K06246]
116697226  flt4; vascular endothelial growth factor receptor 3 isoform X1 [KO:K05097] [EC:2.7.10.1]
116697253  [KO:K05096] [EC:2.7.10.1]
116697380  vegfb; vascular endothelial growth factor B [KO:K05448]
116697416  [KO:K04440] [EC:2.7.11.24]
116697435  xiap; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
116697674  [KO:K06238]
116697722  col4a2; collagen alpha-2(IV) chain isoform X1 [KO:K06237]
116697981  itga4; integrin alpha-4 [KO:K06483]
116698290  gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
116698394  col4a1; LOW QUALITY PROTEIN: collagen alpha-1(IV) chain [KO:K06237]
116698403  itga6; LOW QUALITY PROTEIN: integrin alpha-6 [KO:K06485]
116698421  [KO:K05717]
116698428  col6a3; collagen alpha-3(VI) chain isoform X1 [KO:K06238]
116698492  [KO:K06240]
116698498  [KO:K05730]
116698538  [KO:K12757]
116698567  [KO:K02649]
116698610  rock1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.1]
116698623  tnr; tenascin-R isoform X1 [KO:K06252]
116698657  [KO:K02161]
116698699  [KO:K06238]
116698700  col6a1; LOW QUALITY PROTEIN: collagen alpha-1(VI) chain [KO:K06238]
116698745  [KO:K04448]
116698815  egfr; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
116698830  [KO:K06485]
116698833  [KO:K05719]
116699144  [KO:K00889] [EC:2.7.1.68]
116699195  [KO:K00922] [EC:2.7.1.153]
116699207  [KO:K02649]
116699211  [KO:K00907] [EC:2.7.11.18]
116699273  [KO:K06237]
116699283  [KO:K06237]
116699327  [KO:K05448]
116699372  tnn; tenascin-N [KO:K06252]
116700009  [KO:K16060]
116700186  [KO:K06251]
116700229  [KO:K05733] [EC:2.7.11.1]
116700400  [KO:K04359]
116700588  [KO:K05732]
116700737  [KO:K04438]
116700940  [KO:K17386]
116701018  [KO:K06272] [EC:2.7.11.1]
116701245  [KO:K08131]
116701310  [KO:K02105]
116701464  col1a2; collagen alpha-2(I) chain isoform X1 [KO:K06236]
116701498  col9a2; collagen alpha-2(IX) chain [KO:K08131]
116701571  itgb8; integrin beta-8 [KO:K06591]
116701641  [KO:K05725] [EC:2.7.10.2]
116701654  [KO:K00889] [EC:2.7.1.68]
116701733  [KO:K05692]
116701833  [KO:K04393]
116702284  vegfc; vascular endothelial growth factor C [KO:K05449]
116702297  [KO:K06493]
116702397  grb2; growth factor receptor-bound protein 2 [KO:K04364]
116702478  [KO:K02677] [EC:2.7.11.13]
116702491  [KO:K04392]
116702550  [KO:K06269] [EC:3.1.3.16]
116702937  [KO:K00907] [EC:2.7.11.18]
116703070  prkcb; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
116703074  emp2; epithelial membrane protein 2 [KO:K26256]
116703090  [KO:K10151]
116703151  pdgfa; platelet-derived growth factor subunit A isoform X1 [KO:K04359]
116703178  ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
116703193  actb; actin, cytoplasmic 1 [KO:K05692]
116703217  mylpf; myosin regulatory light chain 2, skeletal muscle isoform [KO:K12758]
116703513  [KO:K06236]
116703557  emp1; epithelial membrane protein 1 [KO:K26255]
116703619  shc4; SHC-transforming protein 4 isoform X1 [KO:K17449]
116703753  [KO:K04371] [EC:2.7.11.24]
116703860  [KO:K00889] [EC:2.7.1.68]
116703876  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
116703898  crkl; crk-like protein [KO:K04438]
116704060  [KO:K04448]
116704085  [KO:K02649]
116704092  vav2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730]
116704267  [KO:K06252]
116704339  rapgef1; LOW QUALITY PROTEIN: rap guanine nucleotide exchange factor 1 [KO:K06277]
116704341  lamc3; laminin subunit gamma-3 [KO:K06247]
116704390  [KO:K17457]
116704435  shc3; SHC-transforming protein 3 [KO:K17448]
116704504  [KO:K07860]
116704583  [KO:K06271]
116704587  [KO:K06252]
116704619  [KO:K07861]
116704770  [KO:K26255]
116704787  itga1; integrin alpha-1 [KO:K06480]
116704791  [KO:K04659]
116704839  [KO:K03853] [EC:3.4.22.53]
116704891  thbs2; thrombospondin-2 isoform X1 [KO:K04659]
116704895  col9a1; collagen alpha-1(IX) chain [KO:K08131]
116705099  [KO:K04456] [EC:2.7.11.1]
116705301  pten; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN isoform X1 [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
116705377  [KO:K05700]
116705432  [KO:K04440] [EC:2.7.11.24]
116705456  [KO:K19662] [EC:2.7.11.13]
116705775  itga9; integrin alpha-9 [KO:K06585]
116705871  [KO:K17388] [EC:2.7.11.1]
116705940  lama4; laminin subunit alpha-4 [KO:K06241]
116705947  fyn; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
116706057  [KO:K16857]
116706203  fn1; fibronectin isoform X1 [KO:K05717]
116706224  vegfa; vascular endothelial growth factor A isoform X1 [KO:K05448]
116706251  pak5; serine/threonine-protein kinase PAK 5 isoform X1 [KO:K05736] [EC:2.7.11.1]
116706431  [KO:K06269] [EC:3.1.3.16]
116706644  [KO:K16859]
116706683  lama2; laminin subunit alpha-2 [KO:K05637]
116707131  bad; bcl2-associated agonist of cell death [KO:K02158]
116707200  [KO:K06269] [EC:3.1.3.16]
116707274  vav1; proto-oncogene vav isoform X1 [KO:K05730]
116707338  col4a6; collagen alpha-6(IV) chain isoform X1 [KO:K06237]
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)
DOI:10.1023/b:biry.0000011649.03634.74
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)
Related
pathway
esp04010  MAPK signaling pathway
esp04060  Cytokine-cytokine receptor interaction
esp04070  Phosphatidylinositol signaling system
esp04110  Cell cycle
esp04310  Wnt signaling pathway
esp04512  ECM-receptor interaction
esp04810  Regulation of actin cytoskeleton
KO pathway
ko04510   

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