KEGG   PATHWAY: hsa04520Help
Entry
hsa04520                    Pathway                                

Name
Adherens junction - Homo sapiens (human)
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
Cellular Processes; Cellular community - eukaryotes
BRITE hierarchy
Pathway map
hsa04520  Adherens junction
hsa04520

Ortholog table
Disease
H00170  Piebaldism
H00647  Ectodermal dysplasia-syndactyly syndrome
H00719  Leprechaunism
H00759  Waardenburg syndrome
H00800  Loeys-Dietz syndrome
H00801  Familial thoracic aortic aneurysm and dissection
H00942  Rabson-Mendenhall syndrome
H00947  Pilomatricoma
H01023  Juvenile polyposis syndrome
H01207  Trigonocephaly
H01228  Insulin-resistant diabetes mellitus with acanthosis nigricans
H01255  Juvenile-onset dystonia
H01274  Growth delay due to insulin-like growth factor I resistance
Drug
D05716  Repifermin (USAN/INN)
D09328  Cixutumumab (USAN)
D09746  Dalotuzumab (USAN)
D09908  Ganitumab (USAN/INN)
D09925  Linsitinib (USAN/INN)
D09941  Onartuzumab (USAN/INN)
D10056  Robatumumab (USAN/INN)
D10173  Tivantinib (JAN/USAN/INN)
D11307  Telisotuzumab (USAN)
D11344  Telisotuzumab vedotin (USAN)
Other DBs
GO: 0005912
Organism
Homo sapiens (human) [GN:hsa]
Gene
5818  NECTIN1; nectin cell adhesion molecule 1 [KO:K06081]
5819  NECTIN2; nectin cell adhesion molecule 2 [KO:K06531]
25945  NECTIN3; nectin cell adhesion molecule 3 [KO:K06592]
81607  NECTIN4; nectin cell adhesion molecule 4 [KO:K06593]
56288  PARD3; par-3 family cell polarity regulator [KO:K04237]
6714  SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
9855  FARP2; FERM, ARH/RhoGEF and pleckstrin domain protein 2 [KO:K06082]
998  CDC42; cell division cycle 42 [KO:K04393]
5879  RAC1; Rac family small GTPase 1 [KO:K04392]
5880  RAC2; Rac family small GTPase 2 [KO:K07860]
5881  RAC3; Rac family small GTPase 3 [KO:K07861]
7454  WAS; WASP actin nucleation promoting factor [KO:K05747]
8976  WASL; WASP like actin nucleation promoting factor [KO:K05747]
8826  IQGAP1; IQ motif containing GTPase activating protein 1 [KO:K16848]
10458  BAIAP2; BAI1 associated protein 2 [KO:K05627]
8936  WASF1; WASP family member 1 [KO:K05753]
10163  WASF2; WASP family member 2 [KO:K05748]
10810  WASF3; WASP family member 3 [KO:K06083]
4301  AFDN; afadin, adherens junction formation factor [KO:K05702]
4008  LMO7; LIM domain 7 [KO:K06084]
117178  SSX2IP; SSX family member 2 interacting protein [KO:K06085]
10580  SORBS1; sorbin and SH3 domain containing 1 [KO:K06086]
87  ACTN1; actinin alpha 1 [KO:K05699]
81  ACTN4; actinin alpha 4 [KO:K05699]
7414  VCL; vinculin [KO:K05700]
7082  TJP1; tight junction protein 1 [KO:K05701]
999  CDH1; cadherin 1 [KO:K05689]
1500  CTNND1; catenin delta 1 [KO:K05690]
1499  CTNNB1; catenin beta 1 [KO:K02105]
29119  CTNNA3; catenin alpha 3 [KO:K05691]
1495  CTNNA1; catenin alpha 1 [KO:K05691]
1496  CTNNA2; catenin alpha 2 [KO:K05691]
60  ACTB; actin beta [KO:K05692]
71  ACTG1; actin gamma 1 [KO:K05692]
387  RHOA; ras homolog family member A [KO:K04513]
5797  PTPRM; protein tyrosine phosphatase receptor type M [KO:K05693] [EC:3.1.3.48]
5787  PTPRB; protein tyrosine phosphatase receptor type B [KO:K05694] [EC:3.1.3.48]
5792  PTPRF; protein tyrosine phosphatase receptor type F [KO:K05695] [EC:3.1.3.48]
5770  PTPN1; protein tyrosine phosphatase non-receptor type 1 [KO:K05696] [EC:3.1.3.48]
5777  PTPN6; protein tyrosine phosphatase non-receptor type 6 [KO:K05697] [EC:3.1.3.48]
5795  PTPRJ; protein tyrosine phosphatase receptor type J [KO:K05698] [EC:3.1.3.48]
1457  CSNK2A1; casein kinase 2 alpha 1 [KO:K03097] [EC:2.7.11.1]
1459  CSNK2A2; casein kinase 2 alpha 2 [KO:K03097] [EC:2.7.11.1]
283106  CSNK2A3; casein kinase 2 alpha 3 [KO:K03097] [EC:2.7.11.1]
1460  CSNK2B; casein kinase 2 beta [KO:K03115]
6932  TCF7; transcription factor 7 [KO:K02620]
83439  TCF7L1; transcription factor 7 like 1 [KO:K04490]
6934  TCF7L2; transcription factor 7 like 2 [KO:K04491]
51176  LEF1; lymphoid enhancer binding factor 1 [KO:K04492]
3480  IGF1R; insulin like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
3643  INSR; insulin receptor [KO:K04527] [EC:2.7.10.1]
4233  MET; MET proto-oncogene, receptor tyrosine kinase [KO:K05099] [EC:2.7.10.1]
1956  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
2064  ERBB2; erb-b2 receptor tyrosine kinase 2 [KO:K05083] [EC:2.7.10.1]
2260  FGFR1; fibroblast growth factor receptor 1 [KO:K04362] [EC:2.7.10.1]
2534  FYN; FYN proto-oncogene, Src family tyrosine kinase [KO:K05703] [EC:2.7.10.2]
7525  YES1; YES proto-oncogene 1, Src family tyrosine kinase [KO:K05705] [EC:2.7.10.2]
5594  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
6591  SNAI2; snail family transcriptional repressor 2 [KO:K05706]
6615  SNAI1; snail family transcriptional repressor 1 [KO:K05707]
7046  TGFBR1; transforming growth factor beta receptor 1 [KO:K04674] [EC:2.7.11.30]
7048  TGFBR2; transforming growth factor beta receptor 2 [KO:K04388] [EC:2.7.11.30]
4087  SMAD2; SMAD family member 2 [KO:K04500]
4088  SMAD3; SMAD family member 3 [KO:K04500]
4089  SMAD4; SMAD family member 4 [KO:K04501]
1387  CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
2033  EP300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
6885  MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
51701  NLK; nemo like kinase [KO:K04468] [EC:2.7.11.24]
2241  FER; FER tyrosine kinase [KO:K08889] [EC:2.7.10.2]
52  ACP1; acid phosphatase 1 [KO:K14394] [EC:3.1.3.48 3.1.3.2]
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
KO pathway
ko04520   

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