Focal adhesion (WP306)

Homo sapiens

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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. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP306 CPTAC Assay Portal]

Authors

Thomas Kelder , Kristina Hanspers , Alex Pico , Egon Willighagen , Zahra Roudbari , Danielle Truong , Marianthi Kalafati , Anders Riutta , Eric Weitz , and Friederike Ehrhart

Activity

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Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

cell adhesion signaling pathway

Participants
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Label Type Compact URI Comment
PIP3 Metabolite hmdb:HMDB0004249
PIP2 Metabolite chebi:18348
MYL5 GeneProduct ensembl:ENSG00000215375
MYLPF GeneProduct ensembl:ENSG00000180209
PDGFRA GeneProduct ncbigene:5156
CAPN2 GeneProduct ensembl:ENSG00000162909
RAC1 GeneProduct ncbigene:5879
LAMA1 GeneProduct ncbigene:284217
COL1A1 GeneProduct ncbigene:1277
MAPK3 GeneProduct ensembl:ENSG00000102882 MAPK4; mitogen-activated protein kinase 4 [EC:2.7.1.-]
VTN GeneProduct ncbigene:7448
HGF GeneProduct ncbigene:3082
SHC3 GeneProduct ncbigene:53358 SHC3; neuronal Sh
THBS3 GeneProduct ncbigene:7059
PIK3R1 GeneProduct ncbigene:5295
FGR GeneProduct ncbigene:2268
BRAF GeneProduct ncbigene:673
ITGB6 GeneProduct ncbigene:3694
ITGA10 GeneProduct ncbigene:8515
COL4A4 GeneProduct ncbigene:1286
THBS1 GeneProduct ncbigene:7057
ILK GeneProduct ncbigene:3611 ILK; integrin-linked kinase [EC:2.7.1.-]
CCND2 GeneProduct ncbigene:894
THBS4 GeneProduct ncbigene:7060
LAMA2 GeneProduct ncbigene:3908
TNR GeneProduct ncbigene:7143
ITGB8 GeneProduct ncbigene:3696
ROCK1 GeneProduct ncbigene:6093
ITGA6 GeneProduct ncbigene:3655
FYN GeneProduct ncbigene:2534 FYN; FYN oncogene related to SRC FGR YES [EC:2.7.1.112]
PPP1R12A GeneProduct ncbigene:4659
TNK2 GeneProduct ncbigene:10188
VAV1 GeneProduct ncbigene:7409
ELK1 GeneProduct ncbigene:2002
PDGFD GeneProduct ncbigene:80310
VEGF GeneProduct ncbigene:7422
MET GeneProduct ncbigene:4233
KDR GeneProduct ncbigene:3791
CRK GeneProduct ncbigene:1398
CTNNB1 GeneProduct ncbigene:1499
ITGA2 GeneProduct ncbigene:3673
RELN GeneProduct ncbigene:5649
ITGA5 GeneProduct ncbigene:3678
MAPK8 GeneProduct ncbigene:5599
PAK3 GeneProduct ncbigene:5063
PARVB GeneProduct ncbigene:29780
ZYX GeneProduct ncbigene:7791 ZYX; zyxin
IBSP GeneProduct ncbigene:3381
SPP1 GeneProduct ncbigene:6696
COL6A2 GeneProduct ncbigene:1292
PTK2 GeneProduct ncbigene:5747 PTK2; PTK2 protein tyrosine kinase 2 [EC:2.7.1.112
JUN GeneProduct ncbigene:3725
PAK6 GeneProduct ncbigene:56924
ITGAV GeneProduct ncbigene:3685
ITGB1 GeneProduct ncbigene:3688
LAMA5 GeneProduct ncbigene:3911
ITGA4 GeneProduct ncbigene:3676
RAF1 GeneProduct ncbigene:5894 RAF1; v-raf-1 murine leukemia viral oncogene homolog 1 [EC:2.7.1.-]
BUB1B-PAK6 GeneProduct ensembl:ENSG00000259288
ITGA2B GeneProduct ncbigene:3674
MAP2K1 GeneProduct ncbigene:5604 MAP2K1; mitogen-activated protein kinase kinase 1 [EC:2.7.1.-]
LAMB1 GeneProduct ncbigene:3912
FIGF GeneProduct ncbigene:2277
FLT1 GeneProduct ncbigene:2321
PDPK1 GeneProduct ncbigene:5170
ERBB2 GeneProduct ncbigene:2064
EGF GeneProduct ncbigene:1950
CAV1 GeneProduct ncbigene:857 CAV1; caveolin 1 caveolae protein 22kD
MYLK GeneProduct ncbigene:4638
CAV3 GeneProduct ncbigene:859 CAV3; caveolin 3
MAPK1 GeneProduct ncbigene:5594 MAPK1; mitogen-activated protein kinase 1 [EC:2.7.1.-]
CHAD GeneProduct ncbigene:1101
BCL2 GeneProduct ncbigene:596
COMP GeneProduct ncbigene:1311
EMP2 GeneProduct ncbigene:2013
TNC GeneProduct ncbigene:3371
LAMC3 GeneProduct ncbigene:10319
CRKL GeneProduct ensembl:ENSG00000099942
SHC1 GeneProduct ncbigene:6464 SHC1; SHC (Src homology 2 domain containing) transforming protein 1
LAMB2 GeneProduct ncbigene:3913
PIK3R3 GeneProduct ensembl:ENSG00000117461
CDC42 GeneProduct ncbigene:998
RAP1B GeneProduct ncbigene:5908 RAP1B; RAP1B member of RAS oncogene family
PTEN GeneProduct ncbigene:5728
LAMA3 GeneProduct ncbigene:3909
ACTB GeneProduct ncbigene:60
GRB2 GeneProduct ncbigene:2885 GRB2; growth factor receptor-bound protein 2
ITGA9 GeneProduct ncbigene:3680
COL4A2 GeneProduct ncbigene:1284
PAK4 GeneProduct ncbigene:10298
CCND1 GeneProduct ncbigene:595
TXK GeneProduct ncbigene:7294
RAC3 GeneProduct ncbigene:5881
TESK2 GeneProduct ncbigene:10420
SRMS GeneProduct ncbigene:6725
COL1A2 GeneProduct ncbigene:1278
MAPK9 GeneProduct ncbigene:5601
ITGA8 GeneProduct ncbigene:8516
VEGFB GeneProduct ncbigene:7423
AKT2 GeneProduct ncbigene:208
COL5A3 GeneProduct ncbigene:50509
PDGFRB GeneProduct ncbigene:5159
VASP GeneProduct ncbigene:7408 VASP; vasodilator-stimulated phosphoprotein
SOS1 GeneProduct ncbigene:6654 SOS1; son of sevenless homolog 1 (Drosophila)
LAMA4 GeneProduct ncbigene:3910
ARHGAP5 GeneProduct ncbigene:394
COL2A1 GeneProduct ncbigene:1280
LAMB3 GeneProduct ncbigene:3914
RAP1A GeneProduct ncbigene:5906 RAP1A; RAP1A member of RAS oncogene family
TNK1 GeneProduct ncbigene:8711
COL5A2 GeneProduct ncbigene:1290
DOCK1 GeneProduct ncbigene:1793 DOCK1; dedicator of cyto-kinesis
ITGB7 GeneProduct ncbigene:3695
COL4A6 GeneProduct ncbigene:1288
XIAP GeneProduct ensembl:ENSG00000101966
PIK3R2 GeneProduct ncbigene:5296
THBS2 GeneProduct ncbigene:7058
HCK GeneProduct ncbigene:3055
IGF1 GeneProduct ncbigene:3479
FLNA GeneProduct ncbigene:2316
GSK3B GeneProduct ncbigene:2932
BLK GeneProduct ncbigene:640
LAMC1 GeneProduct ncbigene:3915
FN1 GeneProduct ncbigene:2335
LAMC2 GeneProduct ncbigene:3918
PGF GeneProduct ncbigene:5228
ITGA3 GeneProduct ncbigene:3675
PIK3CA GeneProduct ncbigene:5290
TNN GeneProduct ncbigene:63923
BIRC3 GeneProduct ncbigene:330
CCND3 GeneProduct ncbigene:896
BIRC2 GeneProduct ncbigene:329
AKT1 GeneProduct ncbigene:207
TNXB GeneProduct ncbigene:7148
PAK1 GeneProduct ncbigene:5058
PXN GeneProduct ncbigene:5829
PIP5K1C GeneProduct ncbigene:23396
BAD GeneProduct ncbigene:572
ITGA1 GeneProduct ensembl:ENSG00000213949
IGF1R GeneProduct ncbigene:3480
ACTN4 GeneProduct ensembl:ENSG00000130402
SRC GeneProduct ncbigene:6714 SRC; v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) [EC:2.7.1.112]
ACTG1 GeneProduct ncbigene:71
HRAS GeneProduct ncbigene:3265
ITGA7 GeneProduct ncbigene:3679
PDGFA GeneProduct ncbigene:5154
BCAR1 GeneProduct ncbigene:9564
VCL GeneProduct ncbigene:7414 VCL; vinculin
CAV2 GeneProduct ncbigene:858 CAV2; caveolin 2
PIK3CB GeneProduct ncbigene:5291
ITGB5 GeneProduct ncbigene:3693
AKT3 GeneProduct ncbigene:10000
STYK1 GeneProduct ncbigene:55359
TLN1 GeneProduct ncbigene:7094
ROCK2 GeneProduct ncbigene:9475
RAC2 GeneProduct ncbigene:5880
PIK3CD GeneProduct ncbigene:5293
PDGFC GeneProduct ncbigene:56034
VWF GeneProduct ncbigene:7450
ITGA11 GeneProduct ncbigene:22801
ITGB4 GeneProduct ncbigene:3691
RAPGEF1 GeneProduct ncbigene:2889
ITGB3 GeneProduct ncbigene:3690
EGFR GeneProduct ncbigene:1956
VEGFC GeneProduct ncbigene:7424
PAK2 GeneProduct ncbigene:5062
DIAPH1 GeneProduct ensembl:ENSG00000131504
PTK6 GeneProduct ncbigene:5753
RHOA GeneProduct ncbigene:387
RASGRF1 GeneProduct ensembl:ENSG00000058335
MYLK2 GeneProduct ncbigene:85366
PDGFB GeneProduct ncbigene:5155
COL4A1 GeneProduct ncbigene:1282
SHC2 GeneProduct ensembl:ENSG00000129946 SHC1; SHC (Src homology 2 domain containing) transforming protein 1
SHC4 GeneProduct ensembl:ENSG00000185634 SHC1; SHC (Src homology 2 domain containing) transforming protein 1
PRKCA GeneProduct ensembl:ENSG00000154229 SRC; v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) [EC:2.7.1.112]
PRKCB GeneProduct ensembl:ENSG00000166501 SRC; v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) [EC:2.7.1.112]
PRKCG GeneProduct ensembl:ENSG00000126583 SRC; v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) [EC:2.7.1.112]
ARHGAP35 GeneProduct ensembl:ENSG00000160007
PPP1R12B GeneProduct ensembl:ENSG00000077157
PPP1R12C GeneProduct ensembl:ENSG00000125503
PPP1CA GeneProduct ensembl:ENSG00000172531
PPP1CB GeneProduct ensembl:ENSG00000213639
PPP1CC GeneProduct ensembl:ENSG00000186298
MYL7 GeneProduct ensembl:ENSG00000106631
MYL10 GeneProduct ensembl:ENSG00000106436
MYL12A GeneProduct ensembl:ENSG00000101608
MYL12B GeneProduct ensembl:ENSG00000118680
MYL2 GeneProduct ensembl:ENSG00000111245
MYL9 GeneProduct ensembl:ENSG00000101335
MYLK3 GeneProduct ensembl:ENSG00000140795
MYLK4 GeneProduct ensembl:ENSG00000145949
ACTN1 GeneProduct ncbigene:87
PARVA GeneProduct ensembl:ENSG00000197702
PARVG GeneProduct ensembl:ENSG00000138964
FLNB GeneProduct ensembl:ENSG00000136068
FLNC GeneProduct ensembl:ENSG00000128591
TLN2 GeneProduct ensembl:ENSG00000171914
MAPK10 GeneProduct ensembl:ENSG00000109339
VAV2 GeneProduct ensembl:ENSG00000160293
VAV3 GeneProduct ensembl:ENSG00000134215

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