KEGG   PATHWAY: ko04510
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
Cellular Processes; Cellular community - eukaryotes
Pathway map
ko04510  Focal adhesion
ko04510

Other DBs
GO: 0005925
Orthology
K00889  PIP5K; 1-phosphatidylinositol-4-phosphate 5-kinase [EC:2.7.1.68]
K00907  MYLK; myosin-light-chain kinase [EC:2.7.11.18]
K00922  PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K01110  PTEN; phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [EC:3.1.3.16 3.1.3.48 3.1.3.67]
K02105  CTNNB1; catenin beta 1
K02158  BAD; Bcl-2-antagonist of cell death
K02161  BCL2; apoptosis regulator Bcl-2
K02649  PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K02677  PRKCA; classical protein kinase C alpha type [EC:2.7.11.13]
K02833  HRAS; GTPase HRas
K03083  GSK3B; glycogen synthase kinase 3 beta [EC:2.7.11.26]
K03099  SOS; son of sevenless
K03853  CAPN2; calpain-2 [EC:3.4.22.53]
K03900  VWF; von Willebrand factor
K04349  RASGRF1; Ras-specific guanine nucleotide-releasing factor 1
K04353  RAP1A; Ras-related protein Rap-1A
K04357  EGF; epidermal growth factor
K04359  PDGFA; platelet-derived growth factor subunit A
K04361  EGFR, ERBB1; epidermal growth factor receptor [EC:2.7.10.1]
K04363  PDGFRA, CD140A; platelet-derived growth factor receptor alpha [EC:2.7.10.1]
K04364  GRB2; growth factor receptor-bound protein 2
K04365  BRAF; B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04366  RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04368  MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04371  ERK, MAPK1_3; mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04375  ELK1; ETS domain-containing protein Elk-1
K04392  RAC1; Ras-related C3 botulinum toxin substrate 1
K04393  CDC42; cell division control protein 42
K04409  PAK1; p21-activated kinase 1 [EC:2.7.11.1]
K04410  PAK2; p21-activated kinase 2 [EC:2.7.11.1]
K04437  FLNA; filamin-A
K04438  CRK, CRKII; C-crk adapter molecule crk
K04440  JNK; mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24]
K04448  JUN; transcription factor AP-1
K04456  AKT; RAC serine/threonine-protein kinase [EC:2.7.11.1]
K04503  CCND1; G1/S-specific cyclin-D1
K04513  RHOA; Ras homolog gene family, member A
K04514  ROCK1; Rho-associated protein kinase 1 [EC:2.7.11.39]
K04659  THBS2S; thrombospondin 2/3/4/5
K04725  XIAP, BIRC4; E3 ubiquitin-protein ligase XIAP [EC:2.3.2.27]
K05083  ERBB2, HER2, CD340; receptor tyrosine-protein kinase erbB-2 [EC:2.7.10.1]
K05087  IGF1R, CD221; insulin-like growth factor 1 receptor [EC:2.7.10.1]
K05089  PDGFRB, CD140B; platelet-derived growth factor receptor beta [EC:2.7.10.1]
K05096  FLT1, VEGFR1; FMS-like tyrosine kinase 1 [EC:2.7.10.1]
K05097  FLT4, VEGFR3; FMS-like tyrosine kinase 4 [EC:2.7.10.1]
K05098  KDR, VEGFR2, CD309; kinase insert domain protein receptor [EC:2.7.10.1]
K05099  MET, HGFR; proto-oncogene tyrosine-protein kinase Met [EC:2.7.10.1]
K05448  VEGFA; vascular endothelial growth factor A
K05449  VEGFC_D; vascular endothelial growth factor C/D
K05450  PDGFC_D; platelet derived growth factor C/D
K05459  IGF1; insulin-like growth factor 1
K05460  HGF; hepatocyte growth factor
K05635  LAMC1; laminin, gamma 1
K05636  LAMB1; laminin, beta 1
K05637  LAMA1_2; laminin, alpha 1/2
K05692  ACTB_G1; actin beta/gamma 1
K05699  ACTN1_4; actinin alpha 1/4
K05700  VCL; vinculin
K05703  FYN; tyrosine-protein kinase Fyn [EC:2.7.10.2]
K05704  SRC; tyrosine-protein kinase Src [EC:2.7.10.2]
K05717  FN1; fibronectin 1
K05719  ITGB1, CD29; integrin beta 1
K05725  PTK2, FAK; focal adhesion kinase 1 [EC:2.7.10.2]
K05726  BCAR1, CAS; breast cancer anti-estrogen resistance 1
K05730  VAV; guanine nucleotide exchange factor VAV
K05732  ARHGAP35, GRLF1; glucocorticoid receptor DNA-binding factor 1
K05733  PAK3, MRX30; p21-activated kinase 3 [EC:2.7.11.1]
K05734  PAK4; p21-activated kinase 4 [EC:2.7.11.1]
K05735  PAK6; p21-activated kinase 6 [EC:2.7.11.1]
K05736  PAK5, PAK7; p21-activated kinase 5 [EC:2.7.11.1]
K05740  DIAPH1; diaphanous 1
K05760  PXN; paxillin
K06236  COL1A; collagen type I alpha
K06237  COL4A; collagen type IV alpha
K06238  COL6A; collagen type VI alpha
K06240  LAMA3_5; laminin, alpha 3/5
K06241  LAMA4; laminin, alpha 4
K06243  LAMB2; laminin, beta 2
K06244  LAMB3; laminin, beta 3
K06245  LAMB4; laminin, beta 4
K06246  LAMC2; laminin, gamma 2
K06247  LAMC3; laminin, gamma 3
K06248  CHAD; chondroadherin
K06249  RELN; reelin [EC:3.4.21.-]
K06250  SPP1, BNSP, OPN; secreted phosphoprotein 1
K06251  VTN; vitronectin
K06252  TN; tenascin
K06253  IBSP; integrin binding sialoprotein
K06269  PPP1C; serine/threonine-protein phosphatase PP1 catalytic subunit [EC:3.1.3.16]
K06270  PPP1R12A, MYPT1; protein phosphatase 1 regulatory subunit 12A
K06271  TLN; talin
K06272  ILK; integrin-linked kinase [EC:2.7.11.1]
K06273  ZYX; zyxin
K06274  VASP; vasodilator-stimulated phosphoprotein
K06275  PARV; parvin
K06276  PDPK1; 3-phosphoinositide dependent protein kinase-1 [EC:2.7.11.1]
K06277  RAPGEF1, GRF2; Rap guanine nucleotide exchange factor 1
K06278  CAV1; caveolin 1
K06279  SHC1; SHC-transforming protein 1
K06476  ITGA2B, CD41; integrin alpha 2B
K06480  ITGA1, CD49a; integrin alpha 1
K06481  ITGA2, CD49b; integrin alpha 2
K06482  ITGA3, CD49c; integrin alpha 3
K06483  ITGA4, CD49d; integrin alpha 4
K06484  ITGA5, CD49e; integrin alpha 5
K06485  ITGA6, CD49f; integrin alpha 6
K06487  ITGAV, CD51; integrin alpha V
K06493  ITGB3, CD61; integrin beta 3
K06525  ITGB4, CD104; integrin beta 4
K06583  ITGA7; integrin alpha 7
K06584  ITGA8; integrin alpha 8
K06585  ITGA9; integrin alpha 9
K06586  ITGA10; integrin alpha 10
K06587  ITGA11; integrin alpha 11
K06588  ITGB5; integrin beta 5
K06589  ITGB6; integrin beta 6
K06590  ITGB7; integrin beta 7
K06591  ITGB8; integrin beta 8
K07836  RAP1B; Ras-related protein Rap-1B
K07860  RAC2; Ras-related C3 botulinum toxin substrate 2
K07861  RAC3; Ras-related C3 botulinum toxin substrate 3
K08131  COL9A; collagen type IX alpha
K10151  CCND2; G1/S-specific cyclin-D2
K10152  CCND3; G1/S-specific cyclin-D3
K10351  MYL2; myosin regulatory light chain 2
K12329  PPP1R12B, MYPT2; protein phosphatase 1 regulatory subunit 12B
K12753  MYL5; myosin regulatory light chain 5
K12754  MYL7; myosin regulatory light chain 7
K12755  MYL9; myosin regulatory light chain 9
K12756  MYL10; myosin regulatory light chain 10
K12757  MYL12; myosin regulatory light chain 12
K12758  MYLPF; fast skeletal myosin light chain 2
K12958  CAV2; caveolin 2
K12959  CAV3; caveolin 3
K13708  DOCK1; dedicator of cytokinesis protein 1
K13709  ARHGAP5; Rho GTPase-activating protein 5
K16060  BIRC2_3; baculoviral IAP repeat-containing protein 2/3
K16857  THBS1; thrombospondin 1
K16858  VEGFB; vascular endothelial growth factor B
K16859  PGF; placenta growth factor
K17386  PDGFB; platelet-derived growth factor subunit B
K17388  ROCK2; Rho-associated protein kinase 2 [EC:2.7.11.39]
K17447  SHC2; SHC-transforming protein 2
K17448  SHC3; SHC-transforming protein 3
K17449  SHC4; SHC-transforming protein 4
K17457  PPP1R12C, MBS85; protein phosphatase 1 regulatory subunit 12C
K19662  PRKCB; classical protein kinase C beta type [EC:2.7.11.13]
K19663  PRKCG; classical protein kinase C gamma type [EC:2.7.11.13]
K19719  COL2A; collagen type II alpha
K26255  EMP1; epithelial membrane protein 1
K26256  EMP2; epithelial membrane protein 2
K27392  FLNB; filamin-B
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
ko04010  MAPK signaling pathway
ko04060  Cytokine-cytokine receptor interaction
ko04070  Phosphatidylinositol signaling system
ko04110  Cell cycle
ko04151  PI3K-Akt signaling pathway
ko04310  Wnt signaling pathway
ko04512  ECM-receptor interaction
ko04810  Regulation of actin cytoskeleton

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