KEGG   PATHWAY: npr04510
Entry
npr04510                    Pathway                                
Name
Focal adhesion - Nanorana parkeri (Xizang Plateau frog)
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
npr04510  Focal adhesion
npr04510

Other DBs
GO: 0005925
Organism
Nanorana parkeri (Xizang Plateau frog) [GN:npr]
Gene
108790501  COL1A2; collagen alpha-2(I) chain [KO:K06236]
108784001  COL1A1; collagen alpha-1(I) chain [KO:K06236]
108800103  COL2A1; collagen alpha-1(II) chain [KO:K19719]
108787443  COL4A1; collagen alpha-1(IV) chain [KO:K06237]
108787444  COL4A2; collagen alpha-2(IV) chain [KO:K06237]
108788810  COL4A6; collagen alpha-6(IV) chain [KO:K06237]
108788813  COL4A5; collagen alpha-5(IV) chain isoform X1 [KO:K06237]
108788853  COL6A1; collagen alpha-1(VI) chain isoform X1 [KO:K06238]
108795802  COL6A6; collagen alpha-6(VI) chain [KO:K06238]
108789838  COL6A3; collagen alpha-3(VI) chain [KO:K06238]
108792064  collagen alpha-6(VI) chain-like [KO:K06238]
108801821  COL6A2; collagen alpha-2(VI) chain isoform X1 [KO:K06238]
108789516  COL9A3; collagen alpha-3(IX) chain [KO:K08131]
108793880  COL9A1; collagen alpha-1(IX) chain [KO:K08131]
108804851  COL9A2; collagen alpha-2(IX) chain [KO:K08131]
108784886  LAMA1; laminin subunit alpha-1 [KO:K05637]
108786894  LAMA2; laminin subunit alpha-2 [KO:K05637]
108789987  LAMA5; laminin subunit alpha-5 [KO:K06240]
108795478  LAMA3; laminin subunit alpha-3 [KO:K06240]
108797114  laminin subunit alpha-4-like [KO:K06241]
108802662  LAMB1; laminin subunit beta-1 [KO:K05636]
108804387  LAMB2; laminin subunit beta-2 [KO:K06243]
108804386  laminin subunit beta-1-like [KO:K06243]
108792087  LAMB3; laminin subunit beta-3 [KO:K06244]
108803213  laminin subunit beta-4-like [KO:K06245]
108802173  laminin subunit beta-4-like [KO:K06245]
108803355  LAMC1; laminin subunit gamma-1 [KO:K05635]
108803366  LAMC2; laminin subunit gamma-2 [KO:K06246]
108796401  CHAD; chondroadherin [KO:K06248]
108795226  reelin-like [KO:K06249] [EC:3.4.21.-]
108790212  RELN; LOW QUALITY PROTEIN: reelin [KO:K06249] [EC:3.4.21.-]
108796832  THBS1; thrombospondin-1 [KO:K16857]
108794774  THBS3; thrombospondin-3 [KO:K04659]
108789855  THBS2; thrombospondin-2 [KO:K04659]
108796348  cartilage oligomeric matrix protein-like [KO:K04659]
108797516  THBS4; thrombospondin-4 [KO:K04659]
108789839  FN1; fibronectin isoform X1 [KO:K05717]
108787538  VTN; vitronectin [KO:K06251]
108786512  TNXB; tenascin-X [KO:K06252]
108786287  tenascin-N-like [KO:K06252]
108786298  tenascin-R-like [KO:K06252]
108805020  TNC; tenascin [KO:K06252]
108792025  VWF; von Willebrand factor [KO:K03900]
108792940  ITGA1; integrin alpha-1 [KO:K06480]
108799979  ITGA2; LOW QUALITY PROTEIN: integrin alpha-2 [KO:K06481]
108785975  integrin alpha-IIb-like [KO:K06476]
108785976  integrin alpha-IIb-like [KO:K06476]
108784022  ITGA3; integrin alpha-3 [KO:K06482]
108789472  ITGA4; integrin alpha-4 [KO:K06483]
108797346  ITGA5; integrin alpha-5 [KO:K06484]
108800541  ITGA6; integrin alpha-6 [KO:K06485]
108796489  ITGA7; integrin alpha-7 [KO:K06583]
108795077  ITGA8; integrin alpha-8 [KO:K06584]
108788067  ITGA9; integrin alpha-9 [KO:K06585]
108800102  integrin alpha-9-like [KO:K06585]
108798333  ITGA10; integrin alpha-10 [KO:K06586]
108784111  ITGA11; integrin alpha-11 [KO:K06587]
108794469  ITGAV; integrin alpha-V isoform X1 [KO:K06487]
108792462  ITGB1; integrin beta-1 [KO:K05719]
108797421  ITGB3; integrin beta-3 [KO:K06493]
108791154  ITGB4; integrin beta-4 isoform X1 [KO:K06525]
108791265  ITGB5; LOW QUALITY PROTEIN: integrin beta-5 [KO:K06588]
108799786  ITGB6; integrin beta-6 [KO:K06589]
108786823  ITGB7; integrin beta-7 [KO:K06590]
108804525  ITGB8; integrin beta-8 [KO:K06591]
108801035  EMP2; epithelial membrane protein 2 [KO:K26256]
108800714  PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359]
108798502  PDGFB; platelet-derived growth factor subunit B [KO:K17386]
108789641  PDGFC; platelet-derived growth factor C [KO:K05450]
108798307  EGF; pro-epidermal growth factor [KO:K04357]
108789614  IGF1; insulin-like growth factor I [KO:K05459]
108800210  VEGFA; vascular endothelial growth factor A [KO:K05448]
108794236  VEGFB; vascular endothelial growth factor B [KO:K05448]
108792318  VEGFD; vascular endothelial growth factor D [KO:K05449]
108792718  VEGFC; vascular endothelial growth factor C [KO:K05449]
108792728  HGF; hepatocyte growth factor [KO:K05460]
108804111  PDGFRA; platelet-derived growth factor receptor alpha isoform X1 [KO:K04363] [EC:2.7.10.1]
108785807  PDGFRB; platelet-derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
108787513  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
108803904  KDR; vascular endothelial growth factor receptor 2 [KO:K05098] [EC:2.7.10.1]
108799381  epidermal growth factor receptor-like [KO:K04361] [EC:2.7.10.1]
108799518  epidermal growth factor receptor-like [KO:K04361] [EC:2.7.10.1]
108791089  vascular endothelial growth factor receptor kdr-like [KO:K05096] [EC:2.7.10.1]
108796337  FLT1; vascular endothelial growth factor receptor 1 [KO:K05096] [EC:2.7.10.1]
108785383  FLT4; vascular endothelial growth factor receptor 3 [KO:K05097] [EC:2.7.10.1]
108788984  MET; hepatocyte growth factor receptor [KO:K05099] [EC:2.7.10.1]
108792756  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
108794300  EMP1; LOW QUALITY PROTEIN: epithelial membrane protein 1 [KO:K26255]
108787987  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
108803391  ARHGAP35; rho GTPase-activating protein 35 [KO:K05732]
108785059  ARHGAP5; LOW QUALITY PROTEIN: rho GTPase-activating protein 5 [KO:K13709]
108789229  transforming protein RhoA [KO:K04513]
108790560  rho-related GTP-binding protein RhoA-D isoform X1 [KO:K04513]
108798735  DIAPH1; protein diaphanous homolog 1 [KO:K05740]
108797185  ROCK1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.39]
108788599  ROCK2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.39]
108788538  MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351]
108796071  MYL7; myosin regulatory light chain 2, atrial isoform [KO:K12754]
108787984  MYL9; myosin regulatory light polypeptide 9 [KO:K12755]
108801753  MYL10; myosin regulatory light chain 10 [KO:K12756]
108784895  myosin regulatory light chain RLC-A [KO:K12757]
108803796  LOW QUALITY PROTEIN: myosin regulatory light chain 2, skeletal muscle isoform-like [KO:K12758]
108796512  serine/threonine-protein phosphatase alpha-2 isoform-like [KO:K06269] [EC:3.1.3.16]
108786345  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
108788527  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
108799788  PPP1R12A; protein phosphatase 1 regulatory subunit 12A [KO:K06270]
108802964  MYLK3; myosin light chain kinase 3 [KO:K00907] [EC:2.7.11.18]
108787381  MYLK4; myosin light chain kinase family member 4 [KO:K00907] [EC:2.7.11.18]
108785969  myosin light chain kinase, smooth muscle-like [KO:K00907] [EC:2.7.11.18]
108794327  PIP5K1C; phosphatidylinositol 4-phosphate 5-kinase type-1 gamma [KO:K00889] [EC:2.7.1.68]
108795209  PIP5K1A; phosphatidylinositol 4-phosphate 5-kinase type-1 alpha [KO:K00889] [EC:2.7.1.68]
108786375  PIP5K1B; phosphatidylinositol 4-phosphate 5-kinase type-1 beta [KO:K00889] [EC:2.7.1.68]
108796718  ACTG1; actin, cytoplasmic 2 [KO:K05692]
108799803  actin, cytoplasmic 1 [KO:K05692]
108791003  RASGRF1; ras-specific guanine nucleotide-releasing factor 1 [KO:K04349]
108787073  CAPN2; calpain-2 catalytic subunit isoform X1 [KO:K03853] [EC:3.4.22.53]
108786661  calpain-2 catalytic subunit-like [KO:K03853] [EC:3.4.22.53]
108804987  ACTN4; alpha-actinin-4 isoform X1 [KO:K05699]
108794113  ACTN1; alpha-actinin-1 isoform X1 [KO:K05699]
108784056  TLN2; talin-2 [KO:K06271]
108803051  talin-1-like [KO:K06271]
108790450  FLNA; filamin-A isoform X1 [KO:K04437]
108791862  FLNB; filamin-B isoform X1 [KO:K27392]
108800100  PXN; paxillin [KO:K05760]
108799886  ILK; integrin-linked protein kinase [KO:K06272] [EC:2.7.11.1]
108784897  ZYX; zyxin [KO:K06273]
108797655  VCL; vinculin isoform X1 [KO:K05700]
108784597  PARVB; beta-parvin [KO:K06275]
108784605  PARVG; gamma-parvin [KO:K06275]
108785978  PARVA; alpha-parvin isoform X1 [KO:K06275]
108794718  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
108794095  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
108787157  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
108801162  GSK3B; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
108790738  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
108791355  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
108797498  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
108792768  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
108785765  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
108796670  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
108798423  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
108797628  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
108802963  phosphatidylinositol 3-kinase regulatory subunit gamma-like [KO:K02649]
108789013  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
108788861  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]
108792057  VAV3; guanine nucleotide exchange factor VAV3 [KO:K05730]
108802048  VAV2; guanine nucleotide exchange factor VAV2 [KO:K05730]
108793527  VAV1; proto-oncogene vav [KO:K05730]
108794473  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
108783678  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
108791334  RAC3; ras-related C3 botulinum toxin substrate 3 [KO:K07861]
108790159  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
108796965  serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
108804973  PAK4; serine/threonine-protein kinase PAK 4 isoform X1 [KO:K05734] [EC:2.7.11.1]
108795532  PAK5; serine/threonine-protein kinase PAK 7 isoform X1 [KO:K05736] [EC:2.7.11.1]
108789294  PAK6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
108797397  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
108796559  BCAR1; breast cancer anti-estrogen resistance protein 1 [KO:K05726]
108801710  CRK; adapter molecule crk isoform X1 [KO:K04438]
108802369  CRKL; crk-like protein isoform X1 [KO:K04438]
108790880  DOCK1; dedicator of cytokinesis protein 1 [KO:K13708]
108795307  RAPGEF1; rap guanine nucleotide exchange factor 1 isoform X1 [KO:K06277]
108789680  RAP1A; ras-related protein Rap-1A [KO:K04353]
108804561  RAP1B; ras-related protein Rap-1b [KO:K07836]
108794648  mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
108804455  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
108788164  JUN; transcription factor AP-1 [KO:K04448]
108793029  BRAF; serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
108788996  CAV1; caveolin-1 [KO:K06278]
108784481  caveolin-2-like [KO:K12958]
108788741  CAV2; caveolin-2 [KO:K12958]
108784486  caveolin-3-like [KO:K12959]
108786026  CAV3; caveolin-3 [KO:K12959]
108790091  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
108795195  SHC1; SHC-transforming protein 1 [KO:K06279]
108790334  SHC2; SHC-transforming protein 2 [KO:K17447]
108792509  SHC3; LOW QUALITY PROTEIN: SHC-transforming protein 3 [KO:K17448]
108792188  SHC4; SHC-transforming protein 4 [KO:K17449]
108791159  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
108788949  SOS1; son of sevenless homolog 1 [KO:K03099]
108795074  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
108786689  HRAS; GTPase HRas [KO:K02833]
108787573  RAF proto-oncogene serine/threonine-protein kinase-like [KO:K04366] [EC:2.7.11.1]
108784101  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
108794889  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
108801239  ELK1; ETS domain-containing protein Elk-1 isoform X1 [KO:K04375]
108793412  G1/S-specific cyclin-D1-like [KO:K04503]
108785450  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
108788361  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
108786933  putative inhibitor of apoptosis [KO:K16060]
108788768  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
108794161  BAD; bcl2-associated agonist of cell death [KO:K02158]
108793666  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
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
npr04010  MAPK signaling pathway
npr04060  Cytokine-cytokine receptor interaction
npr04070  Phosphatidylinositol signaling system
npr04110  Cell cycle
npr04310  Wnt signaling pathway
npr04512  ECM-receptor interaction
npr04810  Regulation of actin cytoskeleton
KO pathway
ko04510   
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