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
PATHWAY_MAP hsa04520  Adherens junction
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)
            D11524  Enfortumab (USAN)
            D11525  Enfortumab vedotin (USAN)
            D11894  Amivantamab (USAN/INN)
            D12287  Terevalefim (USAN/INN)
DBLINKS     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]
            8976  WASL; WASP like actin nucleation promoting factor [KO:K23612]
            7454  WAS; WASP actin nucleation promoting factor [KO:K05747]
            8826  IQGAP1; IQ motif containing GTPase activating protein 1 [KO:K16848]
            10458  BAIAP2; BAR/IMD domain containing adaptor 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]
            71  ACTG1; actin gamma 1 [KO:K05692]
            60  ACTB; actin beta [KO:K05692]
            387  RHOA; ras homolog family member A [KO:K04513]
            52  ACP1; acid phosphatase 1 [KO:K14394] [EC:3.1.3.2 3.1.3.48]
            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]
            2241  FER; FER tyrosine kinase [KO:K08889] [EC:2.7.10.2]
            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]
            4088  SMAD3; SMAD family member 3 [KO:K23605]
            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]
REFERENCE   PMID:15001769
  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   PMID:10204118
  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   PMID:10959047
  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   PMID:15489912
  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   PMID:11171368
  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   PMID:11984870
  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   PMID:12640114
  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   PMID:14623871
  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   PMID:11703922
  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   PMID:12665527
  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   PMID:10890911
  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   PMID:15551862
  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   PMID:15561584
  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
REL_PATHWAY hsa04010  MAPK signaling pathway
            hsa04060  Cytokine-cytokine receptor interaction
            hsa04310  Wnt signaling pathway
            hsa04350  TGF-beta signaling pathway
            hsa04530  Tight junction
            hsa04810  Regulation of actin cytoskeleton
KO_PATHWAY  ko04520
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