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 (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
Drug
D00085  Insulin (JAN/USP)
D04541  Insulin human, isophane (USP)
D04542  Insulin human zinc (USP)
D04543  Insulin human zinc, extended (USP)
D04544  Insulin I 125 (USAN)
D04545  Insulin I 131 (USAN)
D04546  Insulin, dalanated (USAN)
D04547  Insulin, isophane (USP)
D04548  Insulin, neutral (USAN)
D04549  Insulin zinc, extended (USP)
D04550  Insulin zinc, prompt (USP)
D04551  Insulin zinc (USP)
D05622  Proinsulin human (USAN)
D08080  Insulin injection, biphasic isophane (BAN)
D09328  Cixutumumab (USAN)
D09727  Insulin degludec (USAN/INN)
D09746  Dalotuzumab (USAN)
D09908  Ganitumab (USAN/INN)
D09925  Linsitinib (USAN/INN)
D09941  Onartuzumab (USAN/INN)
D10056  Robatumumab (USAN/INN)
Other DBs
BSID: 83070
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; Wiskott-Aldrich syndrome [KO:K05747]
8976  WASL; Wiskott-Aldrich syndrome like [KO:K05747]
8826  IQGAP1; IQ motif containing GTPase activating protein 1 [KO:K16848]
10458  BAIAP2; BAI1 associated protein 2 [KO:K05627]
8936  WASF1; WAS protein family member 1 [KO:K05753]
10163  WASF2; WAS protein family member 2 [KO:K05748]
10810  WASF3; WAS protein 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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