KEGG   PATHWAY: shr04510
Entry
shr04510                    Pathway                                
Name
Focal adhesion - Sarcophilus harrisii (Tasmanian devil)
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
shr04510  Focal adhesion
shr04510

Other DBs
GO: 0005925
Organism
Sarcophilus harrisii (Tasmanian devil) [GN:shr]
Gene
100913231  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
100913262  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100913337  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
100913423  VEGFA; vascular endothelial growth factor A [KO:K05448]
100913539  ITGA8; integrin alpha-8 [KO:K06584]
100913762  ITGB6; integrin beta-6 [KO:K06589]
100913793  THBS2; thrombospondin-2 [KO:K04659]
100913968  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
100914017  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
100914028  [KO:K16060]
100914252  RAPGEF1; rap guanine nucleotide exchange factor 1 isoform X5 [KO:K06277]
100914676  ARHGAP5; rho GTPase-activating protein 5 [KO:K13709]
100914678  ELK1; ETS domain-containing protein Elk-1 [KO:K04375]
100914727  ERBB2; receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
100914800  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
100915068  ILK; integrin-linked protein kinase isoform X1 [KO:K06272] [EC:2.7.11.1]
100915116  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
100915177  COL2A1; collagen alpha-1(II) chain isoform X2 [KO:K19719]
100915278  DOCK1; LOW QUALITY PROTEIN: dedicator of cytokinesis protein 1 [KO:K13708]
100915359  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
100915696  HGF; hepatocyte growth factor isoform X1 [KO:K05460]
100916041  COL1A2; collagen alpha-2(I) chain [KO:K06236]
100916102  PDGFD; platelet-derived growth factor D isoform X1 [KO:K05450]
100916483  CAV2; caveolin-2 [KO:K12958]
100916611  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.39]
100916673  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
100916712  [KO:K05692]
100916741  CAV1; caveolin-1 isoform X1 [KO:K06278]
100916865  ROCK2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.39]
100916999  COL9A1; collagen alpha-1(IX) chain [KO:K08131]
100917007  MET; hepatocyte growth factor receptor [KO:K05099] [EC:2.7.10.1]
100917142  MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351]
100917212  PDGFRB; platelet-derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
100917237  PXN; paxillin [KO:K05760]
100917328  COL4A3; collagen alpha-3(IV) chain [KO:K06237]
100917462  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
100917501  ACTN4; alpha-actinin-4 isoform X1 [KO:K05699]
100917568  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
100917586  COL4A4; collagen alpha-4(IV) chain [KO:K06237]
100917745  SHC2; SHC-transforming protein 2 isoform X1 [KO:K17447]
100917875  PDGFB; platelet-derived growth factor subunit B isoform X2 [KO:K17386]
100917897  MYL9; myosin regulatory light polypeptide 9 [KO:K12755]
100917903  MYL7; myosin regulatory light chain 2, atrial isoform [KO:K12754]
100917987  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100918090  MYLK4; myosin light chain kinase family member 4 isoform X1 [KO:K00907] [EC:2.7.11.18]
100918263  PIP5K1C; phosphatidylinositol 4-phosphate 5-kinase type-1 gamma isoform X1 [KO:K00889] [EC:2.7.1.68]
100918370  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
100918372  VEGFD; vascular endothelial growth factor D [KO:K05449]
100918576  VCL; vinculin isoform X1 [KO:K05700]
100918705  EMP2; epithelial membrane protein 2 [KO:K26256]
100918816  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
100919051  ACTB; actin, cytoplasmic 1 [KO:K05692]
100919163  ITGB4; integrin beta-4 isoform X2 [KO:K06525]
100919185  PARVB; beta-parvin isoform X1 [KO:K06275]
100919264  VAV3; guanine nucleotide exchange factor VAV3 [KO:K05730]
100919323  PAK4; LOW QUALITY PROTEIN: serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
100919651  [KO:K12757]
100919657  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
100919960  CHAD; chondroadherin [KO:K06248]
100920097  [KO:K12757]
100920135  RAP1B; ras-related protein Rap-1b [KO:K07836]
100920192  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
100920428  COL9A3; collagen alpha-3(IX) chain [KO:K08131]
100920489  ITGB7; integrin beta-7 [KO:K06590]
100920526  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
100920576  COL6A6; collagen alpha-6(VI) chain [KO:K06238]
100920660  ZYX; zyxin isoform X1 [KO:K06273]
100920734  ITGB3; integrin beta-3 [KO:K06493]
100920760  RASGRF1; ras-specific guanine nucleotide-releasing factor 1 isoform X1 [KO:K04349]
100920810  COL9A2; LOW QUALITY PROTEIN: collagen alpha-2(IX) chain [KO:K08131]
100920836  COL6A5; collagen alpha-5(VI) chain isoform X1 [KO:K06238]
100921166  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
100921255  LAMC1; laminin subunit gamma-1 [KO:K05635]
100921275  PARVG; gamma-parvin isoform X1 [KO:K06275]
100921360  RELN; reelin isoform X1 [KO:K06249] [EC:3.4.21.-]
100921523  LAMC2; laminin subunit gamma-2 [KO:K06246]
100921899  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
100921931  RHOA; transforming protein RhoA [KO:K04513]
100922222  COL6A3; collagen alpha-3(VI) chain isoform X1 [KO:K06238]
100922223  COL6A1; collagen alpha-1(VI) chain [KO:K06238]
100922413  VEGFB; vascular endothelial growth factor B [KO:K16858]
100922621  CAV3; caveolin-3 [KO:K12959]
100922649  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
100922990  LAMB3; LOW QUALITY PROTEIN: laminin subunit beta-3 [KO:K06244]
100923088  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
100923187  ITGA5; integrin alpha-5 [KO:K06484]
100923199  BAD; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
100923249  COL4A2; collagen alpha-2(IV) chain [KO:K06237]
100923457  PARVA; alpha-parvin [KO:K06275]
100923506  COL4A1; collagen alpha-1(IV) chain [KO:K06237]
100923581  CRKL; crk-like protein [KO:K04438]
100923582  FLNB; filamin-B isoform X1 [KO:K27392]
100923807  [KO:K05692]
100923854  ITGA4; integrin alpha-4 isoform X1 [KO:K06483]
100924022  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
100924158  SPP1; osteopontin [KO:K06250]
100924267  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
100924343  FLNA; filamin-A isoform X1 [KO:K04437]
100924495  LAMA2; laminin subunit alpha-2 isoform X4 [KO:K05637]
100924531  LAMA5; laminin subunit alpha-5 [KO:K06240]
100924604  PAK6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
100924632  ITGA9; integrin alpha-9 [KO:K06585]
100924667  COL1A1; collagen alpha-1(I) chain isoform X1 [KO:K06236]
100924669  RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861]
100924685  IBSP; bone sialoprotein 2 [KO:K06253]
100924961  ACTN1; alpha-actinin-1 isoform X1 [KO:K05699]
100924976  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
100924985  PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359]
100925116  PDGFRA; platelet-derived growth factor receptor alpha isoform X2 [KO:K04363] [EC:2.7.10.1]
100925131  MYLK3; myosin light chain kinase 3 isoform X1 [KO:K00907] [EC:2.7.11.18]
100925192  VTN; vitronectin [KO:K06251]
100925265  PPP1R12B; protein phosphatase 1 regulatory subunit 12B isoform X6 [KO:K12329]
100925440  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100925473  PGF; placenta growth factor [KO:K16859]
100925562  TNC; tenascin isoform X1 [KO:K06252]
100925578  LAMA1; laminin subunit alpha-1 [KO:K05637]
100925674  PIP5K1B; phosphatidylinositol 4-phosphate 5-kinase type-1 beta isoform X1 [KO:K00889] [EC:2.7.1.68]
100925712  ITGA10; integrin alpha-10 isoform X1 [KO:K06586]
100926054  LAMA4; laminin subunit alpha-4 isoform X1 [KO:K06241]
100926184  VAV2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730]
100926529  SRC; proto-oncogene tyrosine-protein kinase Src isoform X3 [KO:K05704] [EC:2.7.10.2]
100926698  THBS1; thrombospondin-1 [KO:K16857]
100926699  [KO:K05733] [EC:2.7.11.1]
100926849  EMP1; epithelial membrane protein 1 [KO:K26255]
100926884  THBS4; thrombospondin-4 [KO:K04659]
100926892  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100926921  SHC1; SHC-transforming protein 1 isoform X4 [KO:K06279]
100926931  PPP1R12A; protein phosphatase 1 regulatory subunit 12A isoform X1 [KO:K06270]
100927147  MYLPF; myosin regulatory light chain 2, skeletal muscle isoform isoform X1 [KO:K12758]
100927189  ITGA7; integrin alpha-7 isoform X2 [KO:K06583]
100927199  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]
100927458  SHC4; SHC-transforming protein 4 isoform X1 [KO:K17449]
100927509  FN1; fibronectin isoform X4 [KO:K05717]
100928148  PDGFC; platelet-derived growth factor C [KO:K05450]
100928240  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
100928302  ACTG1; actin, cytoplasmic 2 [KO:K05692]
100928323  TLN2; talin-2 [KO:K06271]
100928379  ITGA3; integrin alpha-3 isoform X1 [KO:K06482]
100928380  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
100928413  DIAPH1; protein diaphanous homolog 1 isoform X1 [KO:K05740]
100928480  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
100928742  VEGFC; vascular endothelial growth factor C [KO:K05449]
100928883  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
100928896  THBS3; thrombospondin-3 isoform X1 [KO:K04659]
100929053  ITGAV; integrin alpha-V [KO:K06487]
100929086  LAMB1; laminin subunit beta-1 [KO:K05636]
100929091  KDR; vascular endothelial growth factor receptor 2 [KO:K05098] [EC:2.7.10.1]
100929099  ITGA11; integrin alpha-11 [KO:K06587]
100929168  [KO:K02833]
100929219  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
100929811  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
100929969  ITGA1; integrin alpha-1 [KO:K06480]
100930095  TNN; tenascin-N [KO:K06252]
100930114  LAMB4; laminin subunit beta-4 isoform X1 [KO:K06245]
100930353  TNR; tenascin-R isoform X1 [KO:K06252]
100930426  FLT1; vascular endothelial growth factor receptor 1 [KO:K05096] [EC:2.7.10.1]
100930570  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
100930636  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
100930714  PIP5K1A; phosphatidylinositol 4-phosphate 5-kinase type-1 alpha [KO:K00889] [EC:2.7.1.68]
100930815  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
100931009  SOS1; son of sevenless homolog 1 isoform X2 [KO:K03099]
100931469  [KO:K06243]
100931618  COL4A5; collagen alpha-5(IV) chain [KO:K06237]
100931658  VASP; vasodilator-stimulated phosphoprotein isoform X1 [KO:K06274]
100931776  ITGB8; integrin beta-8 isoform X1 [KO:K06591]
100931952  MYL5; myosin light chain 5 isoform X1 [KO:K12753]
100932021  ITGA2B; integrin alpha-IIb [KO:K06476]
100932099  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100932306  FLT4; vascular endothelial growth factor receptor 3 [KO:K05097] [EC:2.7.10.1]
100932383  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
100932708  TNXB; tenascin-X isoform X1 [KO:K06252]
100932749  PAK5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
100932999  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
100933019  PTK2; focal adhesion kinase 1 isoform X6 [KO:K05725] [EC:2.7.10.2]
100933116  TLN1; talin-1 [KO:K06271]
100933131  [KO:K16060]
100933169  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
100933417  COL6A2; LOW QUALITY PROTEIN: collagen alpha-2(VI) chain [KO:K06238]
100933673  VWF; von Willebrand factor [KO:K03900]
100933888  VAV1; proto-oncogene vav isoform X1 [KO:K05730]
100934145  LAMA3; laminin subunit alpha-3 isoform X1 [KO:K06240]
100934330  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100934583  COMP; cartilage oligomeric matrix protein [KO:K04659]
100934666  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
100934801  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
100935037  ARHGAP35; LOW QUALITY PROTEIN: rho GTPase-activating protein 35 [KO:K05732]
100935179  LAMC3; laminin subunit gamma-3 isoform X1 [KO:K06247]
100935202  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
100935225  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
100935230  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
100935403  RAP1A; ras-related protein Rap-1A isoform X2 [KO:K04353]
105749727  ITGA2; integrin alpha-2 [KO:K06481]
105749979  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
111719421  [KO:K06243]
111721183  [KO:K06238]
111721579  [KO:K05096] [EC:2.7.10.1]
116419913  HRAS; GTPase HRas [KO:K02833]
116420956  BCAR1; breast cancer anti-estrogen resistance protein 1 [KO:K05726]
116422035  [KO:K04359]
116422717  PPP1R12C; protein phosphatase 1 regulatory subunit 12C [KO:K17457]
116423462  CRK; adapter molecule crk isoform X1 [KO:K04438]
116423739  JUN; transcription factor AP-1 [KO:K04448]
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
shr04010  MAPK signaling pathway
shr04060  Cytokine-cytokine receptor interaction
shr04070  Phosphatidylinositol signaling system
shr04110  Cell cycle
shr04151  PI3K-Akt signaling pathway
shr04310  Wnt signaling pathway
shr04512  ECM-receptor interaction
shr04810  Regulation of actin cytoskeleton
KO pathway
ko04510   

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