KEGG   PATHWAY: cmk04510
Entry
cmk04510                    Pathway                                
Name
Focal adhesion - Callorhinchus milii (elephant shark)
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
cmk04510  Focal adhesion
cmk04510

Other DBs
GO: 0005925
Organism
Callorhinchus milii (elephant shark) [GN:cmk]
Gene
103190072  collagen alpha-1(I) chain isoform X1 [KO:K06236]
103189947  collagen alpha-1(II) chain isoform X1 [KO:K19719]
103189017  col1a2; collagen alpha-2(I) chain isoform X1 [KO:K19719]
103179614  col4a6; collagen alpha-6(IV) chain [KO:K06237]
103175983  collagen alpha-5(IV) chain [KO:K06237]
103175991  collagen alpha-4(IV) chain [KO:K06237]
103179092  collagen alpha-5(IV) chain [KO:K06237]
103177608  col4a2; collagen alpha-2(IV) chain [KO:K06237]
103177556  collagen alpha-1(IV) chain [KO:K06237]
103176324  LOW QUALITY PROTEIN: collagen alpha-1(VI) chain-like [KO:K06238]
103176328  collagen alpha-6(VI) chain-like [KO:K06238]
103176248  LOW QUALITY PROTEIN: collagen alpha-6(VI) chain [KO:K06238]
103186697  collagen alpha-3(VI) chain [KO:K06238]
103182883  LOW QUALITY PROTEIN: collagen alpha-1(VI) chain [KO:K06238]
103182884  col6a2; collagen alpha-2(VI) chain [KO:K06238]
103181583  collagen alpha-2(VI) chain-like [KO:K06238]
103185601  col9a1b; collagen, type IX, alpha 1b [KO:K08131]
103190453  col9a3; collagen alpha-3(IX) chain [KO:K08131]
103181058  lama1; laminin subunit alpha-1 [KO:K05637]
103182330  lama2; laminin subunit alpha-2 [KO:K05637]
103179715  LOW QUALITY PROTEIN: laminin subunit alpha-3 [KO:K06240]
103186251  lama5; laminin subunit alpha-5 [KO:K06240]
103182579  lama4; laminin subunit alpha-4 [KO:K06241]
103190727  LOW QUALITY PROTEIN: laminin subunit beta-1 [KO:K05636]
103176694  lamb2; laminin subunit beta-2 [KO:K06243]
103176693  lamb2l; LOW QUALITY PROTEIN: laminin subunit beta-2 [KO:K06243]
103182508  lamb3; laminin subunit beta-3 [KO:K06244]
103190193  lamb4; laminin subunit beta-4 [KO:K06245]
103179989  laminin subunit gamma-2 [KO:K05635]
103180069  lamc1; laminin subunit gamma-1 [KO:K05635]
103183090  polyamine-modulated factor 1-binding protein 1-like [KO:K05635]
103183102  lamc3; laminin subunit gamma-3 [KO:K06247]
103175646  chad; chondroadherin [KO:K06248]
103176978  reln; reelin [KO:K06249] [EC:3.4.21.-]
103175202  thbs1b; thrombospondin-1 [KO:K16857]
103174809  thbs2a; thrombospondin-2 [KO:K04659]
103177771  thrombospondin-4 [KO:K04659]
103182059  cartilage oligomeric matrix protein [KO:K04659]
103176556  fn1b; fibronectin 1b isoform X4 [KO:K05717]
103180586  vtn; vitronectin precursor [KO:K06251]
103180587  vitronectin-like [KO:K06251]
103180421  LOW QUALITY PROTEIN: tenascin [KO:K06252]
103184805  LOW QUALITY PROTEIN: tenascin-R [KO:K06252]
103185564  vwf; von Willebrand factor [KO:K03900]
103177841  itga1; integrin alpha-1 [KO:K06480]
103177840  itga2.2; integrin alpha-2 [KO:K06481]
103183847  itga3b; integrin alpha-3b isoform X1 [KO:K06482]
103176505  itga4; integrin alpha-4 [KO:K06483]
103176450  integrin alpha-6 isoform X1 [KO:K06485]
103176576  LOW QUALITY PROTEIN: integrin alpha-6 [KO:K06485]
103176577  LOW QUALITY PROTEIN: integrin alpha-6-like [KO:K06485]
103171972  integrin alpha-7 isoform X1 [KO:K06583]
103187062  itga8; integrin alpha-8 [KO:K06584]
103185506  itga9; integrin alpha-9 [KO:K06585]
103189577  itga11a; integrin alpha-11a [KO:K06587]
103176518  itgav; integrin alpha-V [KO:K06487]
103183810  integrin alpha-8 isoform X1 [KO:K06487]
103188814  integrin beta-1 isoform X1 [KO:K05719]
103187732  integrin beta-3 [KO:K06493]
103175434  itgb4; LOW QUALITY PROTEIN: integrin beta-4 [KO:K06525]
103176393  LOW QUALITY PROTEIN: integrin beta-5 [KO:K06588]
103176359  itgb6; integrin beta-6 isoform X1 [KO:K06589]
103171689  itgb7; integrin beta-7 [KO:K06590]
103185062  itgb8; integrin beta-8 isoform X1 [KO:K06591]
103186070  emp2; epithelial membrane protein 2 [KO:K26256]
103178687  platelet-derived growth factor subunit A isoform X1 [KO:K04359]
103175503  platelet-derived growth factor subunit A [KO:K04359]
103173461  platelet-derived growth factor subunit A-like [KO:K17386]
103182267  pdgfc; platelet-derived growth factor C isoform X1 [KO:K05450]
103185765  pdgfd; platelet-derived growth factor D isoform X2 [KO:K05450]
103180890  egf; pro-epidermal growth factor [KO:K04357]
103179868  igf1; insulin-like growth factor I isoform X1 [KO:K05459]
103179198  vegfab; vascular endothelial growth factor Ab isoform X1 [KO:K05448]
103190808  vascular endothelial growth factor A [KO:K16859]
103177593  vegfd; vascular endothelial growth factor D isoform X1 [KO:K05449]
103180215  vegfc; vascular endothelial growth factor C [KO:K05449]
103184142  vascular endothelial growth factor C-like [KO:K05449]
103177006  hepatocyte growth factor [KO:K05460]
103178167  pdgfra; LOW QUALITY PROTEIN: platelet-derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
103188232  platelet-derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
103188389  igf1ra; insulin-like growth factor 1a receptor [KO:K05087] [EC:2.7.10.1]
103178168  kdr; vascular endothelial growth factor receptor 2 [KO:K05098] [EC:2.7.10.1]
103181270  egfra; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
103178759  kdrl; vascular endothelial growth factor receptor kdr-like [KO:K05096] [EC:2.7.10.1]
103183246  flt1; vascular endothelial growth factor receptor 1 [KO:K05096] [EC:2.7.10.1]
103188224  LOW QUALITY PROTEIN: vascular endothelial growth factor receptor 3 [KO:K05097] [EC:2.7.10.1]
103179355  met; hepatocyte growth factor receptor [KO:K05099] [EC:2.7.10.1]
103183785  erbb2; receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
103171906  tyrosine-protein kinase Src-2 isoform X1 [KO:K05704] [EC:2.7.10.2]
103190406  arhgap35a; rho GTPase-activating protein 35 [KO:K05732]
103178561  arhgap5; rho GTPase-activating protein 5 isoform X1 [KO:K13709]
103176633  rhoa; transforming protein RhoA [KO:K04513]
103182401  rho-related GTP-binding protein RhoA-D [KO:K04513]
103184115  protein diaphanous homolog 1 isoform X1 [KO:K05740]
103181334  protein diaphanous homolog 1-like [KO:K05740]
103183447  rock1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.1]
103180944  rock2a; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.1]
103184326  myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351]
103187953  myosin light chain 5 [KO:K12753]
103187780  myl7; myosin regulatory light chain 2, atrial isoform [KO:K12754]
103171965  myl9; myosin regulatory light polypeptide 9 [KO:K12755]
103188437  LOW QUALITY PROTEIN: myosin regulatory light chain 2B, cardiac muscle isoform [KO:K12756]
103183460  myl12.1; myosin, light chain 12, genome duplicate 1 [KO:K12757]
103189617  ppp1cb; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
103184322  ppp1cc; serine/threonine-protein phosphatase PP1-gamma catalytic subunit A [KO:K06269] [EC:3.1.3.16]
103179091  protein phosphatase 1 regulatory subunit 12B [KO:K12329]
103187745  myosin light chain kinase, smooth muscle isoform X1 [KO:K00907] [EC:2.7.11.18]
103176418  myosin light chain kinase, smooth muscle [KO:K00907] [EC:2.7.11.18]
103176059  mylk3; LOW QUALITY PROTEIN: myosin light chain kinase 3 [KO:K00907] [EC:2.7.11.18]
103188646  mylk4a; myosin light chain kinase 2, skeletal/cardiac muscle isoform X1 [KO:K00907] [EC:2.7.11.18]
103178107  pip5k1bb; phosphatidylinositol 4-phosphate 5-kinase type-1 beta isoform X1 [KO:K00889] [EC:2.7.1.68]
103188137  phosphatidylinositol 4-phosphate 5-kinase type-1 gamma isoform X1 [KO:K00889] [EC:2.7.1.68]
103175484  actg1; actin, cytoplasmic 2 [KO:K05692]
103186865  actb; actin, cytoplasmic 1 [KO:K05692]
103189271  rasgrf1; ras-specific guanine nucleotide-releasing factor 1 isoform X1 [KO:K04349]
103177931  calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
103175234  alpha-actinin-1 isoform X1 [KO:K05699]
103190613  LOW QUALITY PROTEIN: alpha-actinin-1 [KO:K05699]
103187905  tln2b; talin-2 [KO:K06271]
103180996  tln1; talin-1 [KO:K06271]
103190036  filamin-B [KO:K27392]
103188473  uncharacterized protein DDB_G0284459 isoform X1 [KO:K05760]
103181903  vcla; vinculin a isoform X3 [KO:K05700]
103175067  parvaa; alpha-parvin isoform X1 [KO:K06275]
103179374  parvb; beta-parvin isoform X1 [KO:K06275]
103179373  parvg; gamma-parvin [KO:K06275]
103186641  pdpk1a; 3-phosphoinositide-dependent protein kinase 1a isoform X1 [KO:K06276] [EC:2.7.11.1]
103175285  akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103181750  RAC-gamma serine/threonine-protein kinase isoform X4 [KO:K04456] [EC:2.7.11.1]
103174353  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103180204  gsk3ba; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
103183916  ctnnb1; catenin beta-1 [KO:K02105]
103175619  protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
103186617  prkcba; protein kinase C, beta a [KO:K19662] [EC:2.7.11.13]
103181063  ptk2aa; protein tyrosine kinase 2aa isoform X3 [KO:K05725] [EC:2.7.10.2]
103175241  pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
103175843  pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
103184230  pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
103177781  LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
103182064  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
103182762  pik3r3b; phosphoinositide-3-kinase, regulatory subunit 3b (gamma) isoform X1 [KO:K02649]
103180851  ptenb; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
103174755  guanine nucleotide exchange factor VAV3 [KO:K05730]
103182968  vav2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730]
103178707  rac1a; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
103191021  ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
103191023  ras-related C3 botulinum toxin substrate 1 [KO:K04392]
103175476  rac3a; ras-related C3 botulinum toxin substrate 3 [KO:K07861]
103172733  serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
103178926  serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
103186430  pak5; LOW QUALITY PROTEIN: serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
103187528  serine/threonine-protein kinase PAK 6 [KO:K05736] [EC:2.7.11.1]
103181348  cdc42; cell division control protein 42 homolog isoform X1 [KO:K04393]
103176114  breast cancer anti-estrogen resistance protein 1 isoform X1 [KO:K05726]
103174463  crk; adapter molecule crk [KO:K04438]
103180276  dock1; dedicator of cytokinesis protein 1 isoform X1 [KO:K13708]
103184630  rapgef1b; rap guanine nucleotide exchange factor 1b isoform X2 [KO:K06277]
103182425  rap1a; ras-related protein Rap-1A [KO:K04353]
103186117  ras-related protein Rap-1b [KO:K07836]
103180867  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
103185857  mitogen-activated protein kinase 8 isoform X2 [KO:K04440] [EC:2.7.11.24]
103183732  mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
103185297  jun; transcription factor AP-1 [KO:K04448]
103181856  braf; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
103179354  caveolin-1 [KO:K06278]
103176736  caveolin-2 [KO:K12958]
103179353  LOW QUALITY PROTEIN: caveolin-2 [KO:K12958]
103176735  cav3; caveolin-3 [KO:K12959]
103178951  tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
103182043  LOW QUALITY PROTEIN: SHC-transforming protein 2 [KO:K17447]
103182842  SHC-transforming protein 3 [KO:K17448]
103187006  SHC-transforming protein 1 isoform X1 [KO:K17449]
103175438  grb2a; growth factor receptor-bound protein 2a [KO:K04364]
103179222  LOW QUALITY PROTEIN: son of sevenless homolog 1 [KO:K03099]
103175274  sos2; son of sevenless homolog 2 isoform X1 [KO:K03099]
103189080  GTPase HRas [KO:K02833]
121852244  GTPase HRas-like [KO:K02833]
103185022  raf1b; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
103186399  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103188576  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103176639  elk1; ETS domain-containing protein Elk-1 [KO:K04375]
121850328  ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
103182468  G1/S-specific cyclin-D2 isoform X1 [KO:K10151]
103185578  G1/S-specific cyclin-D2 isoform X1 [KO:K10151]
121852060  G1/S-specific cyclin-D2-like [KO:K10151]
103177430  birc2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
103178709  E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
103183201  bcl2a; apoptosis regulator Bcl-2a [KO:K02161]
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
cmk04010  MAPK signaling pathway
cmk04060  Cytokine-cytokine receptor interaction
cmk04070  Phosphatidylinositol signaling system
cmk04110  Cell cycle
cmk04310  Wnt signaling pathway
cmk04512  ECM-receptor interaction
cmk04810  Regulation of actin cytoskeleton
KO pathway
ko04510   
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