KEGG   PATHWAY: rno04510
Entry
rno04510                    Pathway                                

Name
Focal adhesion - Rattus norvegicus (rat)
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
rno04510  Focal adhesion
rno04510

Other DBs
GO: 0005925
Organism
Rattus norvegicus (rat) [GN:rno]
Gene
84352  Col1a2; collagen alpha-2(I) chain precursor [KO:K06236]
29393  Col1a1; collagen alpha-1(I) chain precursor [KO:K06236]
25412  Col2a1; collagen alpha-1(II) chain precursor [KO:K19719]
290905  Col4a1; collagen alpha-1(IV) chain precursor [KO:K06237]
306628  Col4a2; collagen alpha-2(IV) chain [KO:K06237]
363457  Col4a5; collagen alpha-5(IV) chain isoform X2 [KO:K06237]
363265  Col4a3; collagen alpha-3(IV) chain precursor [KO:K06237]
363458  Col4a6; collagen alpha-6(IV) chain isoform X1 [KO:K06237]
315981  Col6a4; collagen alpha-4(VI) chain precursor [KO:K06238]
361821  Col6a2; collagen alpha-2(VI) chain precursor [KO:K06238]
294337  Col6a1; collagen alpha-1(VI) chain [KO:K06238]
315979  Col6a6; collagen alpha-6(VI) chain isoform X1 [KO:K06238]
367313  Col6a3; collagen alpha-3(VI) chain isoform X1 [KO:K06238]
501047  Col6a5; collagen alpha-5(VI) chain isoform X2 [KO:K06238]
305104  Col9a1; collagen alpha-1(IX) chain [KO:K08131]
362584  Col9a2; collagen alpha-2(IX) chain precursor [KO:K08131]
362285  Col9a3; collagen type IX alpha 3 chain precursor [KO:K08131]
309368  Lama2; laminin subunit alpha-2 isoform X1 [KO:K05637]
316758  Lama1; laminin subunit alpha-1 precursor [KO:K05637]
140433  Lama5; laminin subunit alpha-5 precursor [KO:K06240]
307582  Lama3; laminin subunit alpha-3 precursor [KO:K06240]
309816  Lama4; laminin subunit alpha-4 precursor [KO:K06241]
298941  Lamb1; laminin subunit beta-1 isoform X1 [KO:K05636]
25473  Lamb2; laminin subunit beta-2 precursor [KO:K06243]
305078  Lamb3; laminin subunit beta-3 precursor [KO:K06244]
117036  Lamc1; laminin subunit gamma-1 precursor [KO:K05635]
192362  Lamc2; laminin subunit gamma-2 precursor [KO:K06246]
311862  Lamc3; laminin subunit gamma-3 precursor [KO:K06247]
29195  Chad; chondroadherin precursor [KO:K06248]
24718  Reln; reelin precursor [KO:K06249] [EC:3.4.21.-]
445442  Thbs1; thrombospondin-1 precursor [KO:K16857]
25304  Comp; cartilage oligomeric matrix protein precursor [KO:K04659]
29220  Thbs4; thrombospondin-4 precursor [KO:K04659]
292406  Thbs2; thrombospondin-2 precursor [KO:K04659]
681309  Thbs3; thrombospondin-3 precursor [KO:K04659]
25661  Fn1; fibronectin precursor [KO:K05717]
25353  Spp1; osteopontin precursor [KO:K06250]
29169  Vtn; vitronectin precursor [KO:K06251]
25567  Tnr; tenascin-R precursor [KO:K06252]
116640  Tnc; tenascin precursor [KO:K06252]
304913  Tnn; tenascin-N precursor [KO:K06252]
116669  Vwf; von Willebrand factor precursor [KO:K03900]
24477  Ibsp; bone sialoprotein 2 precursor [KO:K06253]
25118  Itga1; integrin alpha-1 precursor [KO:K06480]
170921  Itga2; integrin alpha-2 [KO:K06481]
685269  Itga2b; integrin alpha-IIb [KO:K06476]
360606  Itga3; Integrin alpha-3 isoform 1 [KO:K06482]
311144  Itga4; integrin alpha-4 [KO:K06483]
315346  Itga5; integrin alpha-5 [KO:K06484]
114517  Itga6; integrin alpha-6 precursor [KO:K06485]
81008  Itga7; integrin alpha-7 precursor [KO:K06583]
364786  Itga8; integrin alpha-8 [KO:K06584]
685004  Itga9; integrin alpha-9 isoform X1 [KO:K06585]
310683  Itga10; integrin alpha-10 precursor [KO:K06586]
315744  Itga11; integrin alpha-11 precursor [KO:K06587]
296456  Itgav; integrin alpha-V isoform X1 [KO:K06487]
24511  Itgb1; integrin beta-1 precursor [KO:K05719]
29302  Itgb3; integrin beta-3 precursor [KO:K06493]
25724  Itgb4; integrin beta-4 precursor [KO:K06525]
257645  Itgb5; integrin beta-5 precursor [KO:K06588]
311061  Itgb6; integrin beta-6 precursor [KO:K06589]
25713  Itgb7; integrin beta-7 precursor [KO:K06590]
362800  Itgb8; integrin beta-8 [KO:K06591]
25266  Pdgfa; platelet-derived growth factor subunit A precursor [KO:K04359]
24628  Pdgfb; platelet-derived growth factor subunit B precursor [KO:K17386]
79429  Pdgfc; platelet-derived growth factor C precursor [KO:K05450]
66018  Pdgfd; platelet-derived growth factor D precursor [KO:K05450]
25313  Egf; pro-epidermal growth factor precursor [KO:K04357]
24482  Igf1; insulin-like growth factor I isoform d preproprotein [KO:K05459]
83785  Vegfa; vascular endothelial growth factor A isoform 6 precursor [KO:K05448]
89811  Vegfb; vascular endothelial growth factor B precursor [KO:K16858]
94203  Pgf; placenta growth factor precursor [KO:K16859]
114111  Vegfc; vascular endothelial growth factor C precursor [KO:K05449]
360457  Vegfd; vascular endothelial growth factor D precursor [KO:K05449]
24446  Hgf; hepatocyte growth factor preproprotein [KO:K05460]
25267  Pdgfra; platelet-derived growth factor receptor alpha precursor [KO:K04363] [EC:2.7.10.1]
24629  Pdgfrb; platelet-derived growth factor receptor beta precursor [KO:K05089] [EC:2.7.10.1]
25718  Igf1r; insulin-like growth factor 1 receptor precursor [KO:K05087] [EC:2.7.10.1]
25589  Kdr; vascular endothelial growth factor receptor 2 precursor [KO:K05098] [EC:2.7.10.1]
24329  Egfr; epidermal growth factor receptor precursor [KO:K04361] [EC:2.7.10.1]
54251  Flt1; vascular endothelial growth factor receptor 1 isoform 2 precursor [KO:K05096] [EC:2.7.10.1]
114110  Flt4; vascular endothelial growth factor receptor 3 precursor [KO:K05097] [EC:2.7.10.1]
24553  Met; hepatocyte growth factor receptor precursor [KO:K05099] [EC:2.7.10.1]
24337  Erbb2; receptor tyrosine-protein kinase erbB-2 precursor [KO:K05083] [EC:2.7.10.1]
83805  Src; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
306400  Arhgap35; rho GTPase-activating protein 35 [KO:K05732]
299012  Arhgap5; rho GTPase-activating protein 5 [KO:K13709]
117273  Rhoa; transforming protein RhoA [KO:K04513]
297173  RSA-14-44; ras homolog gene family, member A [KO:K04513]
307483  Diaph1; protein diaphanous homolog 1 [KO:K05740]
81762  Rock1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.1]
25537  Rock2; rho-associated protein kinase 2 [KO:K17388] [EC:2.7.11.1]
363925  Myl2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351]
289759  Myl7; myosin regulatory light chain 2, atrial isoform [KO:K12754]
296313  Myl9; myosin regulatory light polypeptide 9 [KO:K12755]
501831  Myl10; myosin regulatory light chain 10 [KO:K12756]
501203  Myl12a; myosin regulatory light chain RLC-A [KO:K12757]
50685  Myl12b; myosin regulatory light chain 12B [KO:K12757]
24584  Mylpf; myosin regulatory light chain 2, skeletal muscle isoform [KO:K12758]
24668  Ppp1ca; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
24669  Ppp1cc; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform 1 [KO:K06269] [EC:3.1.3.16]
25594  Ppp1cb; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
100363225  disks large homolog 5-like isoform X1 [KO:K06269] [EC:3.1.3.16]
116670  Ppp1r12a; protein phosphatase 1 regulatory subunit 12A [KO:K06270]
304813  Ppp1r12b; protein phosphatase 1 regulatory subunit 12B [KO:K12329]
499076  Ppp1r12c; protein phosphatase 1 regulatory subunit 12C [KO:K17457]
288057  Mylk; myosin light chain kinase, smooth muscle [KO:K00907] [EC:2.7.11.18]
117558  Mylk2; myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
291926  Mylk3; myosin light chain kinase 3 [KO:K00907] [EC:2.7.11.18]
100911165  Mylk4; myosin light chain kinase family member 4 [KO:K00907] [EC:2.7.11.18]
309419  Pip5k1b; phosphatidylinositol 4-phosphate 5-kinase type-1 beta [KO:K00889] [EC:2.7.1.68]
314641  Pip5k1c; phosphatidylinositol 4-phosphate 5-kinase type-1 gamma isoform c [KO:K00889] [EC:2.7.1.68]
365865  Pip5k1a; phosphatidylinositol 4-phosphate 5-kinase type-1 alpha [KO:K00889] [EC:2.7.1.68]
100361457  actin, cytoplasmic 2 [KO:K05692]
81822  Actb; actin, cytoplasmic 1 [KO:K05692]
287876  Actg1; actin, cytoplasmic 2 [KO:K05692]
192213  Rasgrf1; ras-specific guanine nucleotide-releasing factor 1 isoform 1 [KO:K04349]
29154  Capn2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
63836  Actn4; alpha-actinin-4 [KO:K05699]
81634  Actn1; alpha-actinin-1 [KO:K05699]
315776  Tln2; talin-2 isoform X1 [KO:K06271]
313494  Tln1; talin-1 [KO:K06271]
306204  Flnb; filamin-B [KO:K04437]
293860  Flna; filamin-A [KO:K04437]
362332  Flnc; filamin-C [KO:K04437]
360820  Pxn; paxillin [KO:K05760]
170922  Ilk; integrin-linked protein kinase [KO:K06272] [EC:2.7.11.1]
114636  Zyx; zyxin [KO:K06273]
361517  Vasp; vasodilator-stimulated phosphoprotein [KO:K06274]
305679  Vcl; vinculin [KO:K05700]
362973  Parvb; beta-parvin [KO:K06275]
57341  Parva; alpha-parvin [KO:K06275]
689069  Parvg; gamma-parvin [KO:K06275]
81745  Pdpk1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
24185  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
25233  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
29414  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
84027  Gsk3b; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
84353  Ctnnb1; catenin beta-1 [KO:K02105]
24680  Prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
25023  Prkcb; protein kinase C beta type isoform 2 [KO:K19662] [EC:2.7.11.13]
24681  Prkcg; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
25614  Ptk2; focal adhesion kinase 1 [KO:K05725] [EC:2.7.10.2]
85243  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
170911  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
366508  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
25513  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
60664  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
29741  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
50557  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]
25156  Vav1; proto-oncogene vav [KO:K05730]
295378  Vav3; guanine nucleotide exchange factor VAV3 [KO:K05730]
296603  Vav2; guanine nucleotide exchange factor VAV2 [KO:K05730]
363875  Rac1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
366957  Rac2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
29431  Pak1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
29432  Pak2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
29433  Pak3; serine/threonine-protein kinase PAK 3 [KO:K05733] [EC:2.7.11.1]
292756  Pak4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
311450  Pak5; serine/threonine-protein kinase PAK 5 [KO:K05736] [EC:2.7.11.1]
296078  Pak6; serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
64465  Cdc42; cell division control protein 42 homolog [KO:K04393]
25414  Bcar1; breast cancer anti-estrogen resistance protein 1 [KO:K05726]
54245  Crk; adapter molecule crk [KO:K04438]
287942  Crkl; crk-like protein [KO:K04438]
309081  Dock1; dedicator of cytokinesis protein 1 [KO:K13708]
63881  Rapgef1; rap guanine nucleotide exchange factor 1 isoform X19 [KO:K06277]
295347  Rap1a; ras-related protein Rap-1A [KO:K04353]
171337  Rap1b; ras-related protein Rap-1b [KO:K07836]
25272  Mapk10; mitogen-activated protein kinase 10 isoform 2 [KO:K04440] [EC:2.7.11.24]
50658  Mapk9; mitogen-activated protein kinase 9 isoform 2 [KO:K04440] [EC:2.7.11.24]
116554  Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
24516  Jun; transcription factor AP-1 [KO:K04448]
114486  Braf; serine/threonine-protein kinase B-raf isoform X6 [KO:K04365] [EC:2.7.11.1]
25404  Cav1; caveolin-1 isoform alpha [KO:K06278]
363425  Cav2; caveolin-2 [KO:K12958]
29161  Cav3; caveolin-3 [KO:K12959]
25150  Fyn; tyrosine-protein kinase Fyn [KO:K05703] [EC:2.7.10.2]
85385  Shc1; SHC-transforming protein 1 isoform b [KO:K06279]
314612  Shc2; SHC-transforming protein 2 [KO:K17447]
114858  Shc3; SHC-transforming protein 3 [KO:K17448]
679845  Shc4; SHC-transforming protein 4 [KO:K17449]
81504  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
85384  Sos2; son of sevenless homolog 2 [KO:K03099]
313845  Sos1; son of sevenless homolog 1 [KO:K03099]
293621  Hras; GTPase HRas [KO:K02833]
367858  GTPase HRas [KO:K02833]
24703  Raf1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
170851  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
116590  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
50689  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
314436  Elk1; ETS domain-containing protein Elk-1 [KO:K04375]
58919  Ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
64033  Ccnd2; G1/S-specific cyclin-D2 [KO:K10151]
25193  Ccnd3; G1/S-specific cyclin-D3 [KO:K10152]
60371  Birc2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
78971  Birc3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
63879  Xiap; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
64639  Bad; bcl2-associated agonist of cell death [KO:K02158]
24224  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
Compound
C04637  1-Phosphatidyl-D-myo-inositol 4,5-bisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  Authors
Turner CE.
  Title
Paxillin and focal adhesion signalling.
  Journal
Nat Cell Biol 2:E231-6 (2000)
DOI:10.1038/35046659
Reference
  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
rno04010  MAPK signaling pathway
rno04060  Cytokine-cytokine receptor interaction
rno04070  Phosphatidylinositol signaling system
rno04110  Cell cycle
rno04151  PI3K-Akt signaling pathway
rno04310  Wnt signaling pathway
rno04512  ECM-receptor interaction
rno04810  Regulation of actin cytoskeleton
KO pathway
ko04510   

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