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; Cell communication
BRITE hierarchy
Pathway map
Adherens junction
hsa04520

All organismsOrtholog table
Disease
H00170  
Piebaldism
H00626  
Nephrotic syndrome and focal segmental glomerulosclerosis
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)
D03257  
Trastuzumab (genetical recombination) (JAN)
D03297  
Mecasermin (genetical recombination) (JAN)
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  
Isophane insulin injection (aqueous suspension) (JAN)
D04548  
Insulin, neutral (USAN)
D04549  
Insulin zinc, extended (USP)
D04550  
Insulin zinc, prompt (USP)
D04551  
Insulin zinc (USP)
D04870  
Mecasermin rinfabate (USAN/INN)
D05446  
Pertuzumab (genetical recombination) (JAN)
D05622  
Proinsulin human (USAN)
D08080  
Insulin injection, biphasic isophane (BAN)
D09328  
Cixutumumab (USAN)
D09345  
Figitumumab (USAN)
D09727  
Insulin degludec (genetical recombination) (JAN)
D09746  
Dalotuzumab (USAN)
D09908  
Ganitumab (USAN/INN)
D09925  
Linsitinib (USAN/INN)
D09941  
Onartuzumab (genetical recombination) (JAN)
D09980  
Trastuzumab emtansine (genetical recombination) (JAN)
D10018  
Necitumumab (USAN/INN)
D10056  
Robatumumab (USAN/INN)
Other DBs
BSID: 
GO: 
Organism
Homo sapiens (human) [GN:hsa]
Gene
5818  
PVRL1; poliovirus receptor-related 1 (herpesvirus entry mediator C) [KO:K06081]
5819  
PVRL2; poliovirus receptor-related 2 (herpesvirus entry mediator B) [KO:K06531]
25945  
PVRL3; poliovirus receptor-related 3 [KO:K06592]
81607  
PVRL4; poliovirus receptor-related 4 [KO:K06593]
56288  
PARD3; par-3 family cell polarity regulator [KO:K04237]
6714  
SRC; v-src avian sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog [KO:K05704] [EC:2.7.10.2]
9855  
FARP2; FERM, RhoGEF and pleckstrin domain protein 2 [KO:K06082]
998  
CDC42; cell division cycle 42 [KO:K04393]
5879  
RAC1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392]
5880  
RAC2; ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2) [KO:K07860]
5881  
RAC3; ras-related C3 botulinum toxin substrate 3 (rho family, small GTP binding protein Rac3) [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  
MLLT4; myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila) [KO:K05702]
4008  
LMO7; LIM domain 7 [KO:K06084]
117178  
SSX2IP; synovial sarcoma, X breakpoint 2 interacting protein [KO:K06085]
10580  
SORBS1; sorbin and SH3 domain containing 1 [KO:K06086]
87  
ACTN1; actinin, alpha 1 [KO:K05699]
88  
ACTN2; actinin, alpha 2 [KO:K05699]
89  
ACTN3; actinin, alpha 3 [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, type 1, E-cadherin (epithelial) [KO:K05689]
1500  
CTNND1; catenin (cadherin-associated protein), delta 1 [KO:K05690]
1499  
CTNNB1; catenin (cadherin-associated protein), beta 1, 88kDa [KO:K02105]
29119  
CTNNA3; catenin (cadherin-associated protein), alpha 3 [KO:K05691]
1495  
CTNNA1; catenin (cadherin-associated protein), alpha 1, 102kDa [KO:K05691]
1496  
CTNNA2; catenin (cadherin-associated protein), 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 polypeptide [KO:K03097] [EC:2.7.11.1]
1459  
CSNK2A2; casein kinase 2, alpha prime polypeptide [KO:K03097] [EC:2.7.11.1]
1460  
CSNK2B; casein kinase 2, beta polypeptide [KO:K03115]
6932  
TCF7; transcription factor 7 (T-cell specific, HMG-box) [KO:K02620]
83439  
TCF7L1; transcription factor 7-like 1 (T-cell specific, HMG-box) [KO:K04490]
6934  
TCF7L2; transcription factor 7-like 2 (T-cell specific, HMG-box) [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 [KO:K05099] [EC:2.7.10.1]
1956  
EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
2064  
ERBB2; v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 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 oncogene related to SRC, FGR, YES [KO:K05703] [EC:2.7.10.2]
7525  
YES1; v-yes-1 Yamaguchi sarcoma viral oncogene homolog 1 [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 zinc finger 2 [KO:K05706]
6615  
SNAI1; snail family zinc finger 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 II (70/80kDa) [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 (fps/fes related) tyrosine kinase [KO:K08889] [EC:2.7.10.2]
52  
ACP1; acid phosphatase 1, soluble [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)
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)
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)
Reference
  Authors
Reynolds AB, Roczniak-Ferguson A.
  Title
Emerging roles for p120-catenin in cell adhesion and cancer.
  Journal
Oncogene 23:7947-56 (2004)
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)
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)
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)
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)
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)
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)
Reference
  Authors
Nakanishi H, Takai Y.
  Title
Roles of nectins in cell adhesion, migration and polarization.
  Journal
Biol Chem 385:885-92 (2004)
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)
KO pathway
 

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