KEGG   PATHWAY: ko04520Help
Entry
ko04520                     Pathway                                

Name
Adherens junction
Description
Cell-cell adherens junctions (AJs), the most common type of intercellular adhesions, are important for maintaining tissue architecture and cell polarity and can limit cell movement and proliferation. At AJs, E-cadherin serves as an essential cell adhesion molecules (CAMs). The cytoplasmic tail binds beta-catenin, which in turn binds alpha-catenin. Alpha-catenin is associated with F-actin bundles directly and indirectly. The integrity of the cadherin-catenin complex is negatively regulated by phosphorylation of beta-catenin by receptor tyrosine kinases (RTKs) and cytoplasmic tyrosine kinases (Fer, Fyn, Yes, and Src), which leads to dissociation of the cadherin-catenin complex. Integrity of this complex is positively regulated by beta -catenin phosphorylation by casein kinase II, and dephosphorylation by protein tyrosine phosphatases. Changes in the phosphorylation state of beta-catenin affect cell-cell adhesion, cell migration and the level of signaling beta-catenin. Wnt signaling acts as a positive regulator of beta-catenin by inhibiting beta-catenin degradation, which stabilizes beta-catenin, and causes its accumulation. Cadherin may acts as a negative regulator of signaling beta-catenin as it binds beta-catenin at the cell surface and thereby sequesters it from the nucleus. Nectins also function as CAMs at AJs, but are more highly concentrated at AJs than E-cadherin. Nectins transduce signals through Cdc42 and Rac, which reorganize the actin cytoskeleton, regulate the formation of AJs, and strengthen cell-cell adhesion.
Class
09140 Cellular Processes; 09144 Cellular community - eukaryotes
BRITE hierarchy
Pathway map
ko04520  Adherens junction
ko04520

Ortholog table
Disease
H00170  Piebaldism
H00647  Ectodermal dysplasia-syndactyly syndrome (EDSS)
H00719  Leprechaunism
H00759  Waardenburg syndrome (WS)
H00800  Loeys-Dietz syndrome (LDS)
H00801  Familial thoracic aortic aneurysm and dissection (TAAD)
H00942  Rabson-Mendenhall syndrome
H00947  Pilomatricoma
H01023  Juvenile polyposis syndrome
H01207  Trigonocephaly
H01228  Insulin-resistant diabetes mellitus with acanthosis nigricans (IRAN)
H01255  Juvenile-onset dystonia
H01274  Growth delay due to insulin-like growth factor I resistance
Other DBs
BSID: 481
GO: 0005912
Orthology
K06081  poliovirus receptor-related protein 1
K06531  poliovirus receptor-related protein 2
K06592  poliovirus receptor-related protein 3
K06593  poliovirus receptor-related 4
K04237  partitioning defective protein 3
K05704  tyrosine-protein kinase Src [EC:2.7.10.2]
K06082  FERM, RhoGEF and pleckstrin domain protein 2
K04393  cell division control protein 42
K04392  Ras-related C3 botulinum toxin substrate 1
K07860  Ras-related C3 botulinum toxin substrate 2
K07861  Ras-related C3 botulinum toxin substrate 3
K05747  Wiskott-Aldrich syndrome protein
K16848  Ras GTPase-activating-like protein IQGAP1
K05627  BAI1-associated protein 2
K05753  WAS protein family, member 1
K05748  WAS protein family, member 2
K06083  WAS protein family, member 3
K05702  afadin
K06084  F-box protein 20
K06085  synovial sarcoma, X breakpoint 2 interacting protein
K06086  sorbin and SH3 domain containing 1
K05699  actinin alpha 1/4
K05700  vinculin
K05701  tight junction protein 1
K05689  cadherin 1, type 1, E-cadherin
K05690  catenin (cadherin-associated protein), delta 1
K02105  catenin beta 1
K05691  catenin alpha
K05692  actin beta/gamma 1
K04513  Ras homolog gene family, member A
K05693  receptor-type tyrosine-protein phosphatase mu [EC:3.1.3.48]
K05694  receptor-type tyrosine-protein phosphatase beta [EC:3.1.3.48]
K05695  receptor-type tyrosine-protein phosphatase F [EC:3.1.3.48]
K05696  tyrosine-protein phosphatase non-receptor type 1 [EC:3.1.3.48]
K05697  tyrosine-protein phosphatase non-receptor type 6 [EC:3.1.3.48]
K05698  receptor-type tyrosine-protein phosphatase eta [EC:3.1.3.48]
K03097  casein kinase II subunit alpha [EC:2.7.11.1]
K03115  casein kinase II subunit beta
K02620  transcription factor 7
K04490  transcription factor 7-like 1
K04491  transcription factor 7-like 2
K04492  lymphoid enhancer-binding factor 1
K05087  insulin-like growth factor 1 receptor [EC:2.7.10.1]
K04527  insulin receptor [EC:2.7.10.1]
K05099  proto-oncogene tyrosine-protein kinase Met [EC:2.7.10.1]
K04361  epidermal growth factor receptor [EC:2.7.10.1]
K05083  receptor tyrosine-protein kinase erbB-2 [EC:2.7.10.1]
K04362  fibroblast growth factor receptor 1 [EC:2.7.10.1]
K05703  tyrosine-protein kinase Fyn [EC:2.7.10.2]
K05705  tyrosine-protein kinase Yes [EC:2.7.10.2]
K04371  mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K05706  snail 2
K05707  snail 1
K04674  TGF-beta receptor type-1 [EC:2.7.11.30]
K04388  TGF-beta receptor type-2 [EC:2.7.11.30]
K04500  mothers against decapentaplegic homolog 2/3
K04501  mothers against decapentaplegic homolog 4
K04498  E1A/CREB-binding protein [EC:2.3.1.48]
K04427  mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25]
K04468  nemo like kinase [EC:2.7.11.24]
Reference
  Authors
Nelson WJ, Nusse R.
  Title
Convergence of Wnt, beta-catenin, and cadherin pathways.
  Journal
Science 303:1483-7 (2004)
DOI:10.1126/science.1094291
Reference
  Authors
Potter E, Bergwitz C, Brabant G.
  Title
The cadherin-catenin system: implications for growth and differentiation of endocrine tissues.
  Journal
Endocr Rev 20:207-39 (1999)
DOI:10.1210/edrv.20.2.0362
Reference
  Authors
Beavon IR.
  Title
The E-cadherin-catenin complex in tumour metastasis: structure, function and regulation.
  Journal
Eur J Cancer 36:1607-20 (2000)
DOI:10.1016/S0959-8049(00)00158-1
Reference
  Authors
Reynolds AB, Roczniak-Ferguson A.
  Title
Emerging roles for p120-catenin in cell adhesion and cancer.
  Journal
Oncogene 23:7947-56 (2004)
DOI:10.1038/sj.onc.1208161
Reference
  Authors
Angst BD, Marcozzi C, Magee AI.
  Title
The cadherin superfamily: diversity in form and function.
  Journal
J Cell Sci 114:629-41 (2001)
Reference
  Authors
Lilien J, Balsamo J, Arregui C, Xu G.
  Title
Turn-off, drop-out: functional state switching of cadherins.
  Journal
Dev Dyn 224:18-29 (2002)
DOI:10.1002/dvdy.10087
Reference
  Authors
Piedra J, Miravet S, Castano J, Palmer HG, Heisterkamp N, Garcia de Herreros A, Dunach M.
  Title
p120 Catenin-associated Fer and Fyn tyrosine kinases regulate beta-catenin Tyr-142 phosphorylation and beta-catenin-alpha-catenin Interaction.
  Journal
Mol Cell Biol 23:2287-97 (2003)
DOI:10.1128/MCB.23.7.2287-2297.2003
Reference
  Authors
Conacci-Sorrell M, Simcha I, Ben-Yedidia T, Blechman J, Savagner P, Ben-Ze'ev A.
  Title
Autoregulation of E-cadherin expression by cadherin-cadherin interactions: the roles of beta-catenin signaling, Slug, and MAPK.
  Journal
J Cell Biol 163:847-57 (2003)
DOI:10.1083/jcb.200308162
Reference
  Authors
Ciruna B, Rossant J.
  Title
FGF signaling regulates mesoderm cell fate specification and morphogenetic movement at the primitive streak.
  Journal
Dev Cell 1:37-49 (2001)
DOI:10.1016/S1534-5807(01)00017-X
Reference
  Authors
Peinado H, Quintanilla M, Cano A.
  Title
Transforming growth factor beta-1 induces snail transcription factor in epithelial cell lines: mechanisms for epithelial mesenchymal transitions.
  Journal
J Biol Chem 278:21113-23 (2003)
DOI:10.1074/jbc.M211304200
Reference
  Authors
Labbe E, Letamendia A, Attisano L.
  Title
Association of Smads with lymphoid enhancer binding factor 1/T cell-specific factor mediates cooperative signaling by the transforming growth factor-beta and wnt pathways.
  Journal
Proc Natl Acad Sci U S A 97:8358-63 (2000)
DOI:10.1073/pnas.150152697
Reference
  Authors
Nakanishi H, Takai Y.
  Title
Roles of nectins in cell adhesion, migration and polarization.
  Journal
Biol Chem 385:885-92 (2004)
DOI:10.1515/BC.2004.116
Reference
  Authors
Irie K, Shimizu K, Sakisaka T, Ikeda W, Takai Y.
  Title
Roles and modes of action of nectins in cell-cell adhesion.
  Journal
Semin Cell Dev Biol 15:643-56 (2004)
DOI:10.1016/j.semcdb.2004.09.002
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