Focal adhesion (WP188)

Rattus norvegicus

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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.

Authors

Kristina Hanspers , Christine Chichester , Friederike Ehrhart , Egon Willighagen , Martina Summer-Kutmon , and Eric Weitz

Activity

last edited pathway curation

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Organisms

Rattus norvegicus

Communities

Annotations

Pathway Ontology

cell adhesion signaling pathway

Participants

Label Type Compact URI Comment
Thbs4 GeneProduct ncbigene:29220
Tnr GeneProduct ncbigene:25567 tenascin R
Vtn GeneProduct ncbigene:29169 vitronectin
Vwf GeneProduct ncbigene:116669
Lamc1 GeneProduct ncbigene:117036
Col5a3 GeneProduct ncbigene:60379
Egf GeneProduct ncbigene:25313
Figf GeneProduct ncbigene:360457
Hgf GeneProduct ncbigene:24446
Igf1 GeneProduct ncbigene:24482
Pdgfa GeneProduct ncbigene:25266
Pgf GeneProduct ncbigene:94203
Pelo GeneProduct ncbigene:294754
Itga7 GeneProduct ncbigene:81008 integrin, alpha 7
Itgam GeneProduct ncbigene:25021 integrin, alpha M
Itgb1 GeneProduct ncbigene:24511 integrin, beta 1
Itgb2 GeneProduct ncbigene:309684 integrin, beta 2
Itgb4 GeneProduct ncbigene:3691
Itgb6 GeneProduct ncbigene:311061 integrin, beta 6
Itgb7 GeneProduct ncbigene:25713 integrin, beta 7
Rap1a GeneProduct ncbigene:295347 RAP1A; RAP1A member of RAS oncogene family
Rap1b GeneProduct ncbigene:171337 RAP1B; RAP1B member of RAS oncogene family
Shc1 GeneProduct ncbigene:85385 SHC1; SHC (Src homology 2 domain containing) transforming protein 1
Shc3 GeneProduct ncbigene:114858 SHC3; neuronal Sh
Zyx GeneProduct ncbigene:114636 ZYX; zyxin
Cav GeneProduct ncbigene:25404 CAV1; caveolin 1 caveolae protein 22kD
Cav3 GeneProduct ncbigene:29161 CAV3; caveolin 3
Fyn GeneProduct ncbigene:25150 FYN; FYN oncogene related to SRC FGR YES [EC:2.7.1.112]
Grb2 GeneProduct ncbigene:81504 GRB2; growth factor receptor-bound protein 2
Src GeneProduct ncbigene:83805 SRC; v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) [EC:2.7.1.112]
Ilk GeneProduct ncbigene:170922 ILK; integrin-linked kinase [EC:2.7.1.-]
Cav2 GeneProduct ncbigene:363425 CAV2; caveolin 2
Actn1 GeneProduct ncbigene:81634 actinin, alpha 1
Chad GeneProduct ncbigene:29195 chondroadherin
Col2a1 GeneProduct ncbigene:25412 collagen, type II, alpha 1
Col3a1 GeneProduct ncbigene:84032 collagen, type III, alpha 1
Col4a1 GeneProduct ncbigene:290905 collagen, type IV, alpha 1
Col4a4 GeneProduct ncbigene:301562 collagen, type IV, alpha 4
Col5a1 GeneProduct ncbigene:85490 collagen, type V, alpha 1
Col1a1 GeneProduct ncbigene:29393 collagen, type I, alpha 1
Col1a2 GeneProduct ncbigene:84352
Fn1 GeneProduct ncbigene:25661 fibronectin 1
Ibsp GeneProduct ncbigene:24477 integrin-binding sialoprotein
Lamc2 GeneProduct ncbigene:192362 laminin, gamma 2
Reln GeneProduct ncbigene:24718 reelin
Spp1 GeneProduct ncbigene:25353 secreted phosphoprotein 1
Blk GeneProduct ncbigene:364403 BLK proto-oncogene, Src family tyrosine kinase
Egfr GeneProduct ncbigene:24329 epidermal growth factor receptor
Erbb2 GeneProduct ncbigene:24337 v-erb-b2 avian erythroblastic leukemia viral oncogene 2
Fgr GeneProduct ncbigene:79113 FGR proto-oncogene, Src family tyrosine kinase
Flt1 GeneProduct ncbigene:54251 FMS-related tyrosine kinase 1
Hck GeneProduct ncbigene:25734 hemopoietic cell kinase
Igf1r GeneProduct ncbigene:25718 insulin-like growth factor 1 receptor
Met GeneProduct ncbigene:24553 MET proto-oncogene, receptor tyrosine kinase
Pdgfra GeneProduct ncbigene:25267 platelet derived growth factor receptor, alpha polypeptide
Pdgfrb GeneProduct ncbigene:24629 platelet derived growth factor receptor, beta polypeptide
Srms GeneProduct ncbigene:296472 src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristylation sites
Txk GeneProduct ncbigene:305311 TXK tyrosine kinase
Tesk2 GeneProduct ncbigene:170908 testis-specific kinase 2
Tnk2 GeneProduct ncbigene:303882 tyrosine kinase, non-receptor, 2
Araf GeneProduct ncbigene:64363 ARAF1; v-raf murine sarcoma 3611 viral oncogene homolog 1 [EC:2.7.1.-]
Mapk7 GeneProduct ncbigene:114509 MAPK7; mitogen-activated protein kinase 7 [EC:2.7.1.-
Map2k5 GeneProduct ncbigene:29568 MAP2K5; mitogen-activated protein kinase kinase 5 [EC:2.7.1.-]
Map2k6 GeneProduct ncbigene:114495 MAP2K6; mitogen-activated protein kinase kinase 6 [EC:2.7.1.-
Mapk12 GeneProduct ncbigene:60352 MAPK12; mitogen-activated protein kinase 12 [EC:2.7.1.-]
Mapk1 GeneProduct ncbigene:116590 MAPK1; mitogen-activated protein kinase 1 [EC:2.7.1.-]
Mapk6 GeneProduct ncbigene:58840 MAPK6; mitogen-activated protein kinase 6 [EC:2.7.1.-]
Map2k2 GeneProduct ncbigene:58960 MAP2K2; mitogen-activated protein kinase kinase 2 [EC:2.7.1.-]
Map2k3 GeneProduct ncbigene:303200 MAP2K3; mitogen-activated protein kinase kinase 3 [EC:2.7.1.-]
Map2k1 GeneProduct ncbigene:170851 MAP2K1; mitogen-activated protein kinase kinase 1 [EC:2.7.1.-]
Ptk2 GeneProduct ncbigene:25614 PTK2; PTK2 protein tyrosine kinase 2 [EC:2.7.1.112
Arhgap5 GeneProduct ncbigene:299012 Rho GTPase activating protein 5
Rhob GeneProduct ncbigene:64373 ras homolog family member B
Pxn GeneProduct ncbigene:360820 paxillin
Capn1 GeneProduct ncbigene:29153 calpain 1, (mu/I) large subunit
Rhoa GeneProduct ncbigene:117273 ras homolog family member A
Pdpk1 GeneProduct ncbigene:81745 3-phosphoinositide dependent protein kinase-1
Akt1 GeneProduct ncbigene:24185 v-akt murine thymoma viral oncogene homolog 1
Akt2 GeneProduct ncbigene:25233 v-akt murine thymoma viral oncogene homolog 2
Rock1 GeneProduct ncbigene:81762 Rho-associated coiled-coil containing protein kinase 1
Rock2 GeneProduct ncbigene:25537 Rho-associated coiled-coil containing protein kinase 2
Pip5k1c GeneProduct ncbigene:314641 phosphatidylinositol-4-phosphate 5-kinase, type I, gamma
Mylk2 GeneProduct ncbigene:117558 myosin light chain kinase 2
Actb GeneProduct ncbigene:81822 actin, beta
Actg1 GeneProduct ncbigene:287876 actin, gamma 1
Gsk3b GeneProduct ncbigene:84027 glycogen synthase kinase 3 beta
Pik3r1 GeneProduct ncbigene:25513 phosphoinositide-3-kinase, regulatory subunit 1
Pik3r2 GeneProduct ncbigene:29741 phosphoinositide-3-kinase, regulatory subunit 2 (beta)
Pik3cb GeneProduct ncbigene:85243 phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta
Pten GeneProduct ncbigene:50557 phosphatase and tensin homolog
Rac1 GeneProduct ncbigene:363875 ras-related C3 botulinum toxin substrate 1
Rac2 GeneProduct ncbigene:366957 ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2)
Pak1 GeneProduct ncbigene:29431 p21 protein (Cdc42/Rac)-activated kinase 1
Pak3 GeneProduct ncbigene:29433 p21 protein (Cdc42/Rac)-activated kinase 3
Pak2 GeneProduct ncbigene:29432 p21 protein (Cdc42/Rac)-activated kinase 2
Pdgfc GeneProduct ncbigene:79429 platelet derived growth factor C
Vegfa GeneProduct ncbigene:83785 vascular endothelial growth factor A
Vegfb GeneProduct ncbigene:89811 vascular endothelial growth factor B
Vegfc GeneProduct ncbigene:114111 vascular endothelial growth factor C
Bcar1 GeneProduct ncbigene:25414 breast cancer anti-estrogen resistance 1
Crk GeneProduct ncbigene:54245 v-crk avian sarcoma virus CT10 oncogene homolog
Rapgef1 GeneProduct ncbigene:63881 Rap guanine nucleotide exchange factor
Cdc42 GeneProduct ncbigene:64465 cell division cycle 42
Bad GeneProduct ncbigene:64639 BCL2-associated agonist of cell death
Bcl2 GeneProduct ncbigene:24224 B-cell CLL/lymphoma 2
Birc2 GeneProduct ncbigene:60371 baculoviral IAP repeat-containing 2
Birc3 GeneProduct ncbigene:78971 baculoviral IAP repeat-containing 3
Birc4 GeneProduct ncbigene:63879 X-linked inhibitor of apoptosis, also known as Birc4, Api3, riap3
Mapk9 GeneProduct ncbigene:50658 mitogen-activated protein kinase 9
Jun GeneProduct ncbigene:24516 jun proto-oncogene
Ccnd1 GeneProduct ncbigene:58919 cyclin D1
Ccnd2 GeneProduct ncbigene:64033 cyclin D2
Col11a1 GeneProduct ncbigene:25654 collagen, type XI, alpha 1
Col11a2 GeneProduct ncbigene:294279
Col4a2 GeneProduct ncbigene:306628
Col5a2 GeneProduct ncbigene:85250 collagen, type V, alpha 2
Col6a2 GeneProduct ncbigene:361821 collagen, type VI, alpha 2
Comp GeneProduct ncbigene:25304
Lama1 GeneProduct ncbigene:316758
Lama2 GeneProduct ensembl:ENSRNOG00000011134
Lama3 GeneProduct ncbigene:307582 laminin, alpha 3
Lama4 GeneProduct ncbigene:309816 laminin, alpha 4
Lama5 GeneProduct ncbigene:140433 laminin, alpha 5
Lamb1 GeneProduct ncbigene:298941
Lamb2 GeneProduct ncbigene:25473 laminin, beta 2
Lamb3 GeneProduct ncbigene:305078 laminin, beta 3
Thbs1 GeneProduct ncbigene:445442 thrombospondin 1
Thbs2 GeneProduct ncbigene:292406 thrombospondin 2
Thbs3 GeneProduct ncbigene:681309 thrombospondin 3
Tnc GeneProduct ncbigene:116640 tenascin C
Col4a6 GeneProduct ncbigene:363458 collagen, type IV, alpha 6
Tnxb GeneProduct ncbigene:415089 tenascin XB
Tnn GeneProduct ncbigene:304913
Lamc3 GeneProduct ncbigene:311862
Pdgfd GeneProduct ncbigene:66018 platelet derived growth factor D
Pdgfb GeneProduct ncbigene:24628 platelet-derived growth factor beta polypeptide
Kdr GeneProduct ncbigene:25589 kinase insert domain receptor
Ptk6 GeneProduct ncbigene:366275
Styk1 GeneProduct ncbigene:500340
Tnk1 GeneProduct ncbigene:303247
Itgb8 GeneProduct ncbigene:362800
Itgb5 GeneProduct ensembl:ENSRNOG00000001795 integrin, beta 5
Itgb3 GeneProduct ncbigene:29302 integrin, beta 3
Itgae GeneProduct ncbigene:83577 integrin, alpha E
Itgav GeneProduct ncbigene:296456 integrin, alpha V
Itgal GeneProduct ncbigene:308995 integrin, alpha L
Itgad GeneProduct ncbigene:64350 integrin, alpha D
Itgax GeneProduct ncbigene:499271
Itga8 GeneProduct ncbigene:364786 integrin, alpha 8
Itga9 GeneProduct ncbigene:685004 integrin, alpha 9
Itga10 GeneProduct ncbigene:310683
Itga11 GeneProduct ncbigene:315744
Itga2b GeneProduct ncbigene:685269 integrin, alpha 2B
Itga6 GeneProduct ncbigene:114517 integrin, alpha 6
Itga5 GeneProduct ncbigene:315346
Itga4 GeneProduct ncbigene:311144
Itga3 GeneProduct ncbigene:360606
Itga2 GeneProduct ncbigene:685269 integrin, alpha 2B
Farp2 GeneProduct ncbigene:316639
Flna GeneProduct ncbigene:293860 filamin A, alpha
Tln1 GeneProduct ncbigene:313494 talin 1
Pik3ca GeneProduct ncbigene:170911 phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha
Pik3cd GeneProduct ncbigene:366508
Pik3cg GeneProduct ncbigene:298947
Pik3r5 GeneProduct ncbigene:497931
Pik3r4 GeneProduct ncbigene:363131
Mapk8 GeneProduct ncbigene:116554 mitogen-activated protein kinase 8
Ccnd3 GeneProduct ncbigene:25193 cyclin D3
Ctnnb1 GeneProduct ncbigene:84353
Myl6 GeneProduct ncbigene:362816
Diap1 GeneProduct ncbigene:307483
Sos1 GeneProduct ncbigene:313845 SOS1; son of sevenless homolog 1 (Drosophila)
Crk1 GeneProduct ncbigene:81649 mitogen activated protein kinase 14, synonym: Mapk14, RK; Hog; p38; CRK1; CSBP; Exip; Mxi2; CSPB1; Csbp1; Csbp2; Prkm14; Prkm15; Sapk2A; p38Hog; p38alpha
Ha-Ras GeneProduct ncbigene:293621 Harvey rat sarcoma virus oncogene, also known as H-ras, HRAS1, c-H-ras
Parvb GeneProduct ncbigene:362973
Vcl GeneProduct ncbigene:305679 VCL; vinculin
Vasp GeneProduct ncbigene:361517 VASP; vasodilator-stimulated phosphoprotein
Dock1 GeneProduct ncbigene:309081 DOCK1; dedicator of cyto-kinesis
Raf1 GeneProduct ncbigene:24703 RAF1; v-raf-1 murine leukemia viral oncogene homolog 1 [EC:2.7.1.-]
Braf GeneProduct ensembl:ENSRNOG00000010957 BRAF; v-raf murine sarcoma viral oncogene homolog B1 [EC:2.7.1.-]
Braf GeneProduct ensembl:ENSRNOG00000010957 B-Raf proto-oncogene, serine/threonine kinase
Sepp1 GeneProduct ncbigene:29360 SEPP1; selenoprotein P plasma
Mapk4 GeneProduct ncbigene:54268 MAPK4; mitogen-activated protein kinase 4 [EC:2.7.1.-]
Elk1 GeneProduct ncbigene:314436 ELK1, member of ETS oncogene family
Rac3 GeneProduct ensembl:ENSRNOG00000048172 also known as LOC688319, ras-related C3 botulinum toxin substrate 3 (rho family, small GTP binding protein Rac3)
Vav1 GeneProduct ncbigene:25156 vav 1 guanine nucleotide exchange factor
Akt3 GeneProduct ncbigene:29414 v-akt murine thymoma viral oncogene homolog 3
Ppp1r12a GeneProduct ncbigene:116670 protein phosphatase 1, regulatory subunit 12A
Mylk GeneProduct ncbigene:288057
Pak4 GeneProduct ncbigene:292756
Pak6 GeneProduct ncbigene:296078
Pak7 GeneProduct ncbigene:311450

References

  1. The PI3K-PDK1 connection: more than just a road to PKB. Vanhaesebroeck B, Alessi DR. Biochem J. 2000 Mar 15;346 Pt 3(Pt 3):561–76. PubMed Europe PMC Scholia
  2. Rho GTPases: signaling, migration, and invasion. Schmitz AA, Govek EE, Böttner B, Van Aelst L. Exp Cell Res. 2000 Nov 25;261(1):1–12. PubMed Europe PMC Scholia
  3. Paxillin and focal adhesion signalling. Turner CE. Nat Cell Biol. 2000 Dec;2(12):E231-6. PubMed Europe PMC Scholia
  4. Focal adhesions: structure and dynamics. Petit V, Thiery JP. Biol Cell. 2000 Oct;92(7):477–94. PubMed Europe PMC Scholia
  5. Fibronectin, integrins, and growth control. Danen EH, Yamada KM. J Cell Physiol. 2001 Oct;189(1):1–13. PubMed Europe PMC Scholia
  6. The protein kinase B/Akt signalling pathway in human malignancy. Nicholson KM, Anderson NG. Cell Signal. 2002 May;14(5):381–95. PubMed Europe PMC Scholia
  7. Get a ligand, get a life: integrins, signaling and cell survival. Stupack DG, Cheresh DA. J Cell Sci. 2002 Oct 1;115(Pt 19):3729–38. PubMed Europe PMC Scholia
  8. Focal adhesion kinase: the first ten years. Parsons JT. J Cell Sci. 2003 Apr 15;116(Pt 8):1409–16. PubMed Europe PMC Scholia
  9. Interactions between growth factor receptors and adhesion molecules: breaking the rules. Comoglio PM, Boccaccio C, Trusolino L. Curr Opin Cell Biol. 2003 Oct;15(5):565–71. PubMed Europe PMC Scholia
  10. Rho and Rac take center stage. Burridge K, Wennerberg K. Cell. 2004 Jan 23;116(2):167–79. PubMed Europe PMC Scholia
  11. Integrins: structure and signaling. Berman AE, Kozlova NI, Morozevich GE. Biochemistry (Mosc). 2003 Dec;68(12):1284–99. PubMed Europe PMC Scholia
  12. The mechanism of action of the tumour suppressor gene PTEN. Hlobilková A, Knillová J, Bártek J, Lukás J, Kolár Z. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2003 Nov;147(1):19–25. PubMed Europe PMC Scholia
  13. Regulation of E-cadherin expression and beta-catenin/Tcf transcriptional activity by the integrin-linked kinase. Oloumi A, McPhee T, Dedhar S. Biochim Biophys Acta. 2004 Apr 1;1691(1):1–15. PubMed Europe PMC Scholia
  14. Multiple connections link FAK to cell motility and invasion. Schlaepfer DD, Mitra SK. Curr Opin Genet Dev. 2004 Feb;14(1):92–101. PubMed Europe PMC Scholia
  15. Mitogenic signal transduction by integrin- and growth factor receptor-mediated pathways. Lee JW, Juliano R. Mol Cells. 2004 Apr 30;17(2):188–202. PubMed Europe PMC Scholia
  16. Integrin signalling during tumour progression. Guo W, Giancotti FG. Nat Rev Mol Cell Biol. 2004 Oct;5(10):816–26. PubMed Europe PMC Scholia
  17. Focal adhesion kinase: in command and control of cell motility. Mitra SK, Hanson DA, Schlaepfer DD. Nat Rev Mol Cell Biol. 2005 Jan;6(1):56–68. PubMed Europe PMC Scholia