KEGG   PATHWAY: rtem04510
Entry
rtem04510                   Pathway                                
Name
Focal adhesion - Rana temporaria (common 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
rtem04510  Focal adhesion
rtem04510

Other DBs
GO: 0005925
Organism
Rana temporaria (common frog) [GN:rtem]
Gene
120918537  COL1A1; LOW QUALITY PROTEIN: collagen alpha-1(I) chain [KO:K06236]
120939897  COL1A2; collagen alpha-2(I) chain isoform X1 [KO:K06236]
120929392  COL2A1; collagen alpha-1(II) chain isoform X1 [KO:K19719]
120913726  COL4A5; collagen alpha-5(IV) chain isoform X1 [KO:K06237]
120913727  COL4A6; collagen alpha-6(IV) chain isoform X1 [KO:K06237]
120926367  COL4A2; collagen alpha-2(IV) chain [KO:K06237]
120926368  COL4A1; collagen alpha-1(IV) chain [KO:K06237]
120940282  COL6A6; collagen alpha-6(VI) chain [KO:K06238]
120943886  COL6A3; collagen alpha-3(VI) chain isoform X1 [KO:K06238]
120943933  COL6A2; collagen alpha-2(VI) chain isoform X1 [KO:K06238]
120943934  COL6A1; collagen alpha-1(VI) chain [KO:K06238]
120937017  COL9A1; collagen alpha-1(IX) chain [KO:K08131]
120919336  COL9A3; collagen alpha-3(IX) chain [KO:K08131]
120926841  COL9A2; collagen alpha-2(IX) chain [KO:K08131]
120937306  LAMA2; LOW QUALITY PROTEIN: laminin subunit alpha-2 [KO:K05637]
120940882  LAMA1; laminin subunit alpha-1 [KO:K05637]
120918746  LAMA5; laminin subunit alpha-5 isoform X1 [KO:K06240]
120940927  LAMA3; laminin subunit alpha-3 [KO:K06240]
120937223  LAMA4; laminin subunit alpha-4 [KO:K06241]
120931785  LAMB1; laminin subunit beta-1 [KO:K05636]
120945056  laminin subunit beta-4-like [KO:K06243]
120945057  LAMB2; laminin subunit beta-2 [KO:K06243]
120927084  LAMB3; laminin subunit beta-3 isoform X1 [KO:K06244]
120931786  laminin subunit beta-4-like isoform X1 [KO:K06245]
120945827  LAMC1; laminin subunit gamma-1 [KO:K05635]
120945828  LAMC2; laminin subunit gamma-2 [KO:K06246]
120918876  CHAD; chondroadherin [KO:K06248]
120931757  RELN; reelin isoform X1 [KO:K06249] [EC:3.4.21.-]
120920536  THBS1; thrombospondin-1 [KO:K16857]
120937577  THBS2; thrombospondin-2 [KO:K04659]
120929244  THBS4; thrombospondin-4 [KO:K04659]
120913194  cartilage oligomeric matrix protein [KO:K04659]
120943877  FN1; fibronectin isoform X1 [KO:K05717]
120927578  VTN; vitronectin [KO:K06251]
120945855  tenascin-R-like [KO:K06252]
120945857  tenascin-N-like isoform X1 [KO:K06252]
120913063  TNC; LOW QUALITY PROTEIN: tenascin [KO:K06252]
120913239  TNXB; tenascin-X isoform X1 [KO:K06252]
120932631  VWF; von Willebrand factor [KO:K03900]
120915387  bone sialoprotein 2-like isoform X1 [KO:K06253]
120928191  ITGA1; integrin alpha-1 [KO:K06480]
120928209  ITGA2; integrin alpha-2 [KO:K06481]
120918314  integrin alpha-IIb-like [KO:K06476]
120919600  integrin alpha-IIb-like [KO:K06476]
120918923  ITGA3; integrin alpha-3 isoform X1 [KO:K06482]
120943951  ITGA4; integrin alpha-4 [KO:K06483]
120929370  ITGA5; integrin alpha-5 [KO:K06484]
120944012  ITGA6; integrin alpha-6 isoform X1 [KO:K06485]
120929559  ITGA7; integrin alpha-7 isoform X1 [KO:K06583]
120939945  ITGA8; integrin alpha-8 [KO:K06584]
120940431  ITGA9; integrin alpha-9 [KO:K06585]
120920139  ITGA10; integrin alpha-10 [KO:K06586]
120931090  ITGA11; integrin alpha-11 [KO:K06587]
120913140  ITGAV; integrin alpha-V [KO:K06487]
120940054  integrin beta-1-A isoform X1 [KO:K05719]
120940052  integrin beta-1-A-like [KO:K05719]
120940053  integrin beta-1-A-like [KO:K05719]
120919174  ITGB3; integrin beta-3 [KO:K06493]
120918677  ITGB4; integrin beta-4 isoform X1 [KO:K06525]
120944288  ITGB5; integrin beta-5 [KO:K06588]
120944078  ITGB6; integrin beta-6 [KO:K06589]
120929312  ITGB7; integrin beta-7 [KO:K06590]
120940146  ITGB8; integrin beta-8 [KO:K06591]
120943581  EMP2; epithelial membrane protein 2 [KO:K26256]
120943462  PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359]
120945372  PDGFB; platelet-derived growth factor subunit B [KO:K17386]
120929043  PDGFD; platelet-derived growth factor D [KO:K05450]
120920251  PDGFC; platelet-derived growth factor C [KO:K05450]
120917738  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
120932128  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
120938083  VEGFA; vascular endothelial growth factor A isoform X1 [KO:K05448]
120921090  VEGFC; vascular endothelial growth factor C [KO:K05449]
120927767  VEGFD; vascular endothelial growth factor D [KO:K05449]
120931733  HGF; hepatocyte growth factor isoform X1 [KO:K05460]
120922903  PDGFRA; platelet-derived growth factor receptor alpha isoform X1 [KO:K04363] [EC:2.7.10.1]
120932546  PDGFRB; platelet-derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
120931158  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
120922871  KDR; vascular endothelial growth factor receptor 2 [KO:K05098] [EC:2.7.10.1]
120940364  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
120929198  FLT1; vascular endothelial growth factor receptor 1 [KO:K05096] [EC:2.7.10.1]
120913770  vascular endothelial growth factor receptor kdr-like [KO:K05096] [EC:2.7.10.1]
120932539  FLT4; vascular endothelial growth factor receptor 3 isoform X1 [KO:K05097] [EC:2.7.10.1]
120931873  MET; hepatocyte growth factor receptor [KO:K05099] [EC:2.7.10.1]
120918450  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
120945461  EMP1; epithelial membrane protein 1 [KO:K26255]
120918772  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
120914390  ARHGAP35; rho GTPase-activating protein 35 [KO:K05732]
120921087  ARHGAP5; LOW QUALITY PROTEIN: rho GTPase-activating protein 5 [KO:K13709]
120913910  transforming protein RhoA-like [KO:K04513]
120927051  rho-related GTP-binding protein RhoC [KO:K04513]
120944999  RHOA; transforming protein RhoA [KO:K04513]
120932484  DIAPH1; protein diaphanous homolog 1 isoform X1 [KO:K05740]
120940912  ROCK1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.1]
120936332  ROCK2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.1]
120933222  MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351]
120933061  MYL7; myosin regulatory light chain 2, atrial isoform [KO:K12754]
120918762  MYL9; myosin regulatory light polypeptide 9 [KO:K12755]
120927620  MYL10; myosin regulatory light chain 10 [KO:K12756]
120940894  myosin regulatory light chain RLC-A [KO:K12757]
120923266  MYLPF; myosin regulatory light chain 2, skeletal muscle isoform [KO:K12758]
120938146  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
120943131  serine/threonine-protein phosphatase alpha-2 isoform-like [KO:K06269] [EC:3.1.3.16]
120933345  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
120931940  PPP1R12A; protein phosphatase 1 regulatory subunit 12A [KO:K06270]
120917244  protein phosphatase 1 regulatory subunit 12A-like isoform X1 [KO:K06270]
120915347  PPP1R12C; protein phosphatase 1 regulatory subunit 12C isoform X1 [KO:K17457]
120917880  MYLK3; myosin light chain kinase 3 isoform X1 [KO:K00907] [EC:2.7.11.18]
120918827  MYLK2; myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
120940648  MYLK4; myosin light chain kinase family member 4 isoform X1 [KO:K00907] [EC:2.7.11.18]
120944282  MYLK; myosin light chain kinase, smooth muscle isoform X1 [KO:K00907] [EC:2.7.11.18]
120910543  PIP5K1C; phosphatidylinositol 4-phosphate 5-kinase type-1 gamma isoform X1 [KO:K00889] [EC:2.7.1.68]
120920620  PIP5K1A; phosphatidylinositol 4-phosphate 5-kinase type-1 alpha [KO:K00889] [EC:2.7.1.68]
120943556  PIP5K1B; phosphatidylinositol 4-phosphate 5-kinase type-1 beta isoform X1 [KO:K00889] [EC:2.7.1.68]
120919014  ACTG1; actin, cytoplasmic 2 [KO:K05692]
120943679  ACTB; actin, cytoplasmic 1 [KO:K05692]
120931069  RASGRF1; ras-specific guanine nucleotide-releasing factor 1 isoform X1 [KO:K04349]
120937867  calpain-2 catalytic subunit-like [KO:K03853] [EC:3.4.22.53]
120913392  calpain-2 catalytic subunit-like [KO:K03853] [EC:3.4.22.53]
120920927  ACTN1; alpha-actinin-1 isoform X1 [KO:K05699]
120913420  ACTN4; alpha-actinin-4 isoform X1 [KO:K05699]
120931521  TLN2; talin-2 isoform X1 [KO:K06271]
120924751  TLN1; talin-1 isoform X1 [KO:K06271]
120924763  talin-1-like [KO:K06271]
120913186  FLNA; filamin-A isoform X1 [KO:K04437]
120945226  FLNB; filamin-B isoform X1 [KO:K27392]
120937302  PXN; paxillin isoform X1 [KO:K05760]
120928861  ILK; integrin-linked protein kinase [KO:K06272] [EC:2.7.11.1]
120946870  ZYX; zyxin [KO:K06273]
120914379  vasodilator-stimulated phosphoprotein isoform X1 [KO:K06274]
120909049  VCL; vinculin isoform X1 [KO:K05700]
120932938  PARVG; gamma-parvin [KO:K06275]
120932939  PARVB; beta-parvin isoform X1 [KO:K06275]
120916986  PARVA; alpha-parvin [KO:K06275]
120943428  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
120920339  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
120913289  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
120928103  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
120940346  CTNNB1; catenin beta-1 [KO:K02105]
120919232  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
120943296  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
120915291  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
120941562  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
120915689  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
120936566  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
120936771  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
120928855  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
120923203  phosphatidylinositol 3-kinase regulatory subunit gamma-like [KO:K02649]
120916053  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
120947094  PTEN; LOW QUALITY PROTEIN: 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]
120913816  VAV2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730]
120926790  VAV1; proto-oncogene vav [KO:K05730]
120945601  VAV3; guanine nucleotide exchange factor VAV3 isoform X1 [KO:K05730]
120943487  ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
120943488  ras-related C3 botulinum toxin substrate 1-like [KO:K04392]
120945320  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
120918911  RAC3; ras-related C3 botulinum toxin substrate 3 [KO:K07861]
120928894  PAK1; serine/threonine-protein kinase PAK 1 isoform X1 [KO:K04409] [EC:2.7.11.1]
120936442  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
120913716  PAK3; serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
120913431  PAK4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
120938049  PAK5; serine/threonine-protein kinase PAK 5 isoform X1 [KO:K05736] [EC:2.7.11.1]
120920285  serine/threonine-protein kinase PAK 6-like [KO:K05735] [EC:2.7.11.1]
120915621  CDC42; LOW QUALITY PROTEIN: cell division control protein 42 homolog [KO:K04393]
120917637  BCAR1; breast cancer anti-estrogen resistance protein 1 isoform X1 [KO:K05726]
120927613  CRK; adapter molecule crk isoform X1 [KO:K04438]
120936703  CRKL; crk-like protein [KO:K04438]
120946747  DOCK1; dedicator of cytokinesis protein 1 isoform X1 [KO:K13708]
120913998  RAPGEF1; rap guanine nucleotide exchange factor 1 isoform X1 [KO:K06277]
120927068  RAP1A; ras-related protein Rap-1A [KO:K04353]
120931994  RAP1B; ras-related protein Rap-1b [KO:K07836]
120909277  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
120915815  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
120946091  JUN; transcription factor AP-1 [KO:K04448]
120932891  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
120931874  CAV1; caveolin-1 isoform X1 [KO:K06278]
120931876  CAV2; caveolin-2 [KO:K12958]
120914414  caveolin-2-like [KO:K12958]
120913206  caveolin-3-like [KO:K12959]
120944800  CAV3; caveolin-3 [KO:K12959]
120937220  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
120920621  SHC1; SHC-transforming protein 1 [KO:K06279]
120910109  SHC2; SHC-transforming protein 2 [KO:K17447]
120941594  SHC3; LOW QUALITY PROTEIN: SHC-transforming protein 3 [KO:K17448]
120931328  SHC4; SHC-transforming protein 4 [KO:K17449]
120918896  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
120937496  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
120920685  SOS2; son of sevenless homolog 2 [KO:K03099]
120917364  HRAS; GTPase HRas [KO:K02833]
120945285  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
120931107  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
120936184  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
120913974  ELK1; ETS domain-containing protein Elk-1 isoform X1 [KO:K04375]
120916056  G1/S-specific cyclin-D1-like [KO:K04503]
120917108  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
120932645  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
120927190  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
120929024  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
120913744  E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
120917599  BAD; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
120940635  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
rtem04010  MAPK signaling pathway
rtem04060  Cytokine-cytokine receptor interaction
rtem04070  Phosphatidylinositol signaling system
rtem04110  Cell cycle
rtem04310  Wnt signaling pathway
rtem04512  ECM-receptor interaction
rtem04810  Regulation of actin cytoskeleton
KO pathway
ko04510   
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