KEGG   PATHWAY: setr04510
Entry
setr04510                   Pathway                                
Name
Focal adhesion - Suncus etruscus (white-toothed pygmy shrew)
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
setr04510  Focal adhesion
setr04510

Other DBs
GO: 0005925
Organism
Suncus etruscus (white-toothed pygmy shrew) [GN:setr]
Gene
125994825  [KO:K04393]
125995101  PTEN; 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]
125995947  MYLK4; myosin light chain kinase family member 4 [KO:K00907] [EC:2.7.11.18]
125995979  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
125996232  TNXB; LOW QUALITY PROTEIN: tenascin-X [KO:K06252]
125996266  VEGFA; vascular endothelial growth factor A [KO:K05448]
125997373  RAP1A; ras-related protein Rap-1A isoform X1 [KO:K04353]
125997407  VAV3; LOW QUALITY PROTEIN: guanine nucleotide exchange factor VAV3 [KO:K05730]
125997479  [KO:K00889] [EC:2.7.1.68]
125997828  THBS4; thrombospondin-4 [KO:K04659]
125997902  [KO:K06238]
125997903  COL6A5; collagen alpha-5(VI) chain [KO:K06238]
125998044  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
125998095  CAV3; caveolin-3 [KO:K12959]
125998190  ITGA9; integrin alpha-9 [KO:K06585]
125998218  [KO:K06238]
125998383  ARHGAP5; rho GTPase-activating protein 5 isoform X1 [KO:K13709]
125998704  [KO:K04393]
125998737  VEGFD; vascular endothelial growth factor D [KO:K05449]
125999018  SOS2; son of sevenless homolog 2 [KO:K03099]
125999067  COL4A5; collagen alpha-5(IV) chain [KO:K06237]
125999073  FLNA; filamin-A isoform X1 [KO:K04437]
125999096  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
125999215  ELK1; ETS domain-containing protein Elk-1 [KO:K04375]
125999512  PAK3; serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
126000963  ITGA1; LOW QUALITY PROTEIN: integrin alpha-1 [KO:K06480]
126001121  COL4A3; collagen alpha-3(IV) chain [KO:K06237]
126001240  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
126001270  ITGB4; integrin beta-4 [KO:K06525]
126001296  EMP2; epithelial membrane protein 2 [KO:K26256]
126001552  PIK3R1; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
126001649  COL4A4; collagen alpha-4(IV) chain [KO:K06237]
126001843  ITGA2; integrin alpha-2 [KO:K06481]
126003375  SHC3; SHC-transforming protein 3 [KO:K17448]
126003432  PDGFC; platelet-derived growth factor C [KO:K05450]
126003551  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
126003668  ROCK1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.1]
126003803  [KO:K12757]
126003804  [KO:K12757]
126003979  ACTN1; alpha-actinin-1 isoform X1 [KO:K05699]
126004091  PGF; placenta growth factor [KO:K16859]
126004175  PPP1R12B; protein phosphatase 1 regulatory subunit 12B isoform X1 [KO:K12329]
126004304  LAMB3; laminin subunit beta-3 [KO:K06244]
126004466  LAMA1; laminin subunit alpha-1 [KO:K05637]
126004489  LAMA3; laminin subunit alpha-3 [KO:K06240]
126004531  PIP5K1B; phosphatidylinositol 4-phosphate 5-kinase type-1 beta isoform X1 [KO:K00889] [EC:2.7.1.68]
126004843  MET; hepatocyte growth factor receptor isoform X1 [KO:K05099] [EC:2.7.10.1]
126005036  CAV2; caveolin-2 [KO:K12958]
126005084  CAV1; caveolin-1 [KO:K06278]
126005849  LAMA2; laminin subunit alpha-2 [KO:K05637]
126005876  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
126005910  LAMA4; laminin subunit alpha-4 [KO:K06241]
126006274  PARVB; beta-parvin [KO:K06275]
126006293  PARVG; gamma-parvin [KO:K06275]
126006376  PDGFB; platelet-derived growth factor subunit B [KO:K17386]
126006381  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
126006387  [KO:K07836]
126006402  PDGFRB; platelet-derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
126006454  VTN; vitronectin [KO:K06251]
126006504  VWF; LOW QUALITY PROTEIN: von Willebrand factor [KO:K03900]
126006674  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
126007180  VEGFC; vascular endothelial growth factor C [KO:K05449]
126008496  HGF; hepatocyte growth factor isoform X1 [KO:K05460]
126008537  LAMC3; laminin subunit gamma-3 [KO:K06247]
126008557  COL6A3; collagen alpha-3(VI) chain [KO:K06238]
126008603  CHAD; chondroadherin [KO:K06248]
126008620  ITGA4; integrin alpha-4 [KO:K06483]
126008648  TLN1; talin-1 isoform X1 [KO:K06271]
126008753  TLN2; talin-2 isoform X1 [KO:K06271]
126008895  ITGAV; integrin alpha-V [KO:K06487]
126009024  ITGB6; integrin beta-6 isoform X1 [KO:K06589]
126009161  ITGA6; integrin alpha-6 [KO:K06485]
126009330  VAV2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730]
126009430  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
126009589  RAPGEF1; rap guanine nucleotide exchange factor 1 [KO:K06277]
126009681  TNC; tenascin [KO:K06252]
126010754  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
126010979  JUN; transcription factor Jun [KO:K04448]
126011041  ZYX; zyxin [KO:K06273]
126011086  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
126011308  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
126011402  COL9A2; collagen alpha-2(IX) chain [KO:K08131]
126011501  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
126012035  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
126012036  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
126012201  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
126013193  FLNB; filamin-B isoform X1 [KO:K27392]
126013242  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
126013352  TNR; tenascin-R isoform X1 [KO:K06252]
126013417  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
126013535  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
126013539  ACTG1; actin, cytoplasmic 2 [KO:K05692]
126013731  RAC3; ras-related C3 botulinum toxin substrate 3 [KO:K07861]
126013935  COL9A3; collagen alpha-3(IX) chain [KO:K08131]
126013943  ITGB1; integrin beta-1 [KO:K05719]
126013961  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
126014007  LAMB2; laminin subunit beta-2 [KO:K06243]
126014129  RHOA; LOW QUALITY PROTEIN: transforming protein RhoA [KO:K04513]
126014167  LAMA5; laminin subunit alpha-5 [KO:K06240]
126014205  ITGA8; LOW QUALITY PROTEIN: integrin alpha-8 [KO:K06584]
126014268  LAMC2; laminin subunit gamma-2 [KO:K06246]
126014269  LAMC1; LOW QUALITY PROTEIN: laminin subunit gamma-1 [KO:K05635]
126014279  TNN; tenascin-N [KO:K06252]
126015550  COL4A2; collagen alpha-2(IV) chain isoform X1 [KO:K06237]
126015551  COL4A1; collagen alpha-1(IV) chain [KO:K06237]
126015663  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
126015747  FLT4; vascular endothelial growth factor receptor 3 [KO:K05097] [EC:2.7.10.1]
126015921  FLT1; vascular endothelial growth factor receptor 1 [KO:K05096] [EC:2.7.10.1]
126016039  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
126016055  PDGFD; platelet-derived growth factor D isoform X1 [KO:K05450]
126016077  ITGA11; integrin alpha-11 [KO:K06587]
126016078  [KO:K16060]
126016368  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
126016471  ITGA3; integrin alpha-3 [KO:K06482]
126017297  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
126017330  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
126017460  MYL9; myosin regulatory light polypeptide 9 [KO:K12755]
126017532  [KO:K04409] [EC:2.7.11.1]
126017569  MYLK2; myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
126017861  BAD; bcl2-associated agonist of cell death [KO:K02158]
126017939  VEGFB; vascular endothelial growth factor B isoform X1 [KO:K16858]
126018108  PAK5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
126018161  ILK; integrin-linked protein kinase [KO:K06272] [EC:2.7.11.1]
126018299  [KO:K04393]
126019001  PARVA; alpha-parvin [KO:K06275]
126019027  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
126019074  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
126019084  HRAS; GTPase HRas [KO:K02833]
126020007  SHC4; SHC-transforming protein 4 [KO:K17449]
126020216  ITGA2B; LOW QUALITY PROTEIN: integrin alpha-IIb [KO:K06476]
126020271  ITGB3; integrin beta-3 [KO:K06493]
126020533  COL1A1; collagen alpha-1(I) chain [KO:K06236]
126020600  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
126020678  ITGA10; integrin alpha-10 isoform X1 [KO:K06586]
126020709  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
126020790  THBS3; thrombospondin-3 [KO:K04659]
126020938  CTNNB1; catenin beta-1 [KO:K02105]
126021156  CRK; LOW QUALITY PROTEIN: adapter molecule crk [KO:K04438]
126021814  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
126021897  RAP1B; ras-related protein Rap-1b [KO:K07836]
126021920  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
126022310  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
126022325  COL2A1; collagen alpha-1(II) chain isoform X1 [KO:K19719]
126022427  [KO:K04410] [EC:2.7.11.1]
126022448  EMP1; epithelial membrane protein 1 [KO:K26255]
126022461  PPP1R12A; protein phosphatase 1 regulatory subunit 12A [KO:K06270]
126022467  ITGB7; integrin beta-7 [KO:K06590]
126022672  ITGA5; integrin alpha-5 [KO:K06484]
126022691  RASGRF1; ras-specific guanine nucleotide-releasing factor 1 [KO:K04349]
126022791  RELN; reelin [KO:K06249] [EC:3.4.21.-]
126022799  LAMB1; laminin subunit beta-1 [KO:K05636]
126022964  ITGA7; integrin alpha-7 isoform X1 [KO:K06583]
126023861  PPP1CB; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
126023864  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
126023916  FN1; fibronectin [KO:K05717]
126024093  ROCK2; rho-associated protein kinase 2 [KO:K17388] [EC:2.7.11.1]
126024665  [KO:K04393]
126024712  THBS2; thrombospondin-2 [KO:K04659]
126024722  PAK6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
126024735  COL1A2; LOW QUALITY PROTEIN: collagen alpha-2(I) chain [KO:K06236]
126024782  THBS1; thrombospondin-1 [KO:K16857]
126025667  COL6A2; collagen alpha-2(VI) chain [KO:K06238]
126025689  COL6A1; collagen alpha-1(VI) chain [KO:K06238]
126025997  ITGB8; integrin beta-8 [KO:K06591]
126026177  ITGB5; integrin beta-5 [KO:K06588]
126026205  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
126026245  MYLK; myosin light chain kinase, smooth muscle [KO:K00907] [EC:2.7.11.18]
126027351  BCAR1; breast cancer anti-estrogen resistance protein 1 isoform X1 [KO:K05726]
126027570  EGF; pro-epidermal growth factor [KO:K04357]
126027586  ACTN4; alpha-actinin-4 isoform X1 [KO:K05699]
126027603  PAK4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
126027949  DIAPH1; protein diaphanous homolog 1 [KO:K05740]
126027978  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
126028082  PPP1R12C; protein phosphatase 1 regulatory subunit 12C [KO:K17457]
126028133  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
126028192  ARHGAP35; rho GTPase-activating protein 35 [KO:K05732]
126028397  MYLK3; myosin light chain kinase 3 [KO:K00907] [EC:2.7.11.18]
126028574  VASP; vasodilator-stimulated phosphoprotein [KO:K06274]
126028736  [KO:K04393]
126029893  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
126030200  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
126030342  COMP; cartilage oligomeric matrix protein [KO:K04659]
126030397  PIP5K1C; phosphatidylinositol 4-phosphate 5-kinase type-1 gamma isoform X1 [KO:K00889] [EC:2.7.1.68]
126030444  ACTB; actin, cytoplasmic 1 [KO:K05692]
126030482  PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359]
126030488  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
126030593  PXN; paxillin isoform X1 [KO:K05760]
126030826  SHC2; SHC-transforming protein 2 [KO:K17447]
126030845  VCL; vinculin isoform X1 [KO:K05700]
126030861  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
126030983  MYL11; myosin regulatory light chain 11 [KO:K12758]
126031078  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
126031105  MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform isoform X1 [KO:K10351]
126031136  VAV1; proto-oncogene vav isoform X1 [KO:K05730]
126031404  MYL7; myosin regulatory light chain 2, atrial isoform [KO:K12754]
126032054  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
126032061  IBSP; bone sialoprotein 2 [KO:K06253]
126032076  SPP1; osteopontin [KO:K06250]
126032296  KDR; vascular endothelial growth factor receptor 2 [KO:K05098] [EC:2.7.10.1]
126032431  PDGFRA; platelet-derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
126033346  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
126033605  DOCK1; dedicator of cytokinesis protein 1 [KO:K13708]
126033690  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
126033704  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
126033713  CRKL; crk-like protein [KO:K04438]
Compound
C04637  1-Phosphatidyl-D-myo-inositol 4,5-bisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
PMID:14756624
  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
PMID:15179030
  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
PMID:11573199
  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
PMID:15459662
  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
PMID:11229600
  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
PMID:12235283
  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
PMID:12640026
  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
PMID:15688067
  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
PMID:14519391
  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
PMID:15108811
  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
PMID:14744429
  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
PMID:11082269
  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
PMID:10698680
  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
PMID:11882383
  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
PMID:15053919
  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
PMID:11146675
  Authors
Turner CE.
  Title
Paxillin and focal adhesion signalling.
  Journal
Nat Cell Biol 2:E231-6 (2000)
DOI:10.1038/35046659
Reference
PMID:15034601
  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
setr04010  MAPK signaling pathway
setr04060  Cytokine-cytokine receptor interaction
setr04070  Phosphatidylinositol signaling system
setr04110  Cell cycle
setr04151  PI3K-Akt signaling pathway
setr04310  Wnt signaling pathway
setr04512  ECM-receptor interaction
setr04810  Regulation of actin cytoskeleton
KO pathway
ko04510   

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