PATHWAY: ko04520 Help
Entry 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 Cellular Processes; Cellular community - eukaryotesBRITE hierarchy
Pathway map Other DBs Orthology K02620 TCF7, TCF-1; transcription factor 7
K03115 CSNK2B; casein kinase II subunit beta
K04237 PARD3; partitioning defective protein 3
K04353 RAP1A; Ras-related protein Rap-1A
K04362 FGFR1, CD331; fibroblast growth factor receptor 1 [EC:2.7.10.1 ]
K04392 RAC1; Ras-related C3 botulinum toxin substrate 1
K04393 CDC42; cell division control protein 42
K04427 MAP3K7, TAK1; mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25 ]
K04490 TCF7L1; transcription factor 7-like 1
K04491 TCF7L2; transcription factor 7-like 2
K04492 LEF1; lymphoid enhancer-binding factor 1
K04501 SMAD4; mothers against decapentaplegic homolog 4
K04513 RHOA; Ras homolog gene family, member A
K05083 ERBB2, HER2, CD340; receptor tyrosine-protein kinase erbB-2 [EC:2.7.10.1 ]
K05087 IGF1R, CD221; insulin-like growth factor 1 receptor [EC:2.7.10.1 ]
K05099 MET, HGFR; proto-oncogene tyrosine-protein kinase Met [EC:2.7.10.1 ]
K05627 BAIAP2, IRSP53; BAI1-associated protein 2
K05689 CDH1, CDHE, CD324; cadherin 1, type 1, E-cadherin
K05690 CTNND1; catenin (cadherin-associated protein), delta 1
K05692 ACTB_G1; actin beta/gamma 1
K05693 PTPRM; receptor-type tyrosine-protein phosphatase mu [EC:3.1.3.48 ]
K05694 PTPRB, PTPB; receptor-type tyrosine-protein phosphatase beta [EC:3.1.3.48 ]
K05695 PTPRF, LAR; receptor-type tyrosine-protein phosphatase F [EC:3.1.3.48 ]
K05696 PTPN1, PTP1B; tyrosine-protein phosphatase non-receptor type 1 [EC:3.1.3.48 ]
K05697 PTPN6, SHP1; tyrosine-protein phosphatase non-receptor type 6 [EC:3.1.3.48 ]
K05698 PTPRJ, DEP1, CD148; receptor-type tyrosine-protein phosphatase eta [EC:3.1.3.48 ]
K05699 ACTN1_4; actinin alpha 1/4
K05701 TJP1, ZO1; tight junction protein 1
K05747 WAS; Wiskott-Aldrich syndrome protein
K05748 WASF2; WAS protein family, member 2
K05753 WASF1; WAS protein family, member 1
K06081 NECTIN1, PVRL1, CD111; poliovirus receptor-related protein 1
K06082 FARP2, FRG; FERM, RhoGEF and pleckstrin domain protein 2
K06083 WASF3; WAS protein family, member 3
K06084 LMO7, FBXO20; F-box protein 20
K06085 SSX2IP, ADIP; synovial sarcoma, X breakpoint 2 interacting protein
K06086 SORBS1, SH3D5, PONSIN, CAP; sorbin and SH3 domain containing protein 1
K06531 NECTIN2, PVRL2, CD112; poliovirus receptor-related protein 2
K06533 CDH5, CD144; cadherin 5, type 2, VE-cadherin
K06592 NECTIN3, PVRL3, CD113; poliovirus receptor-related protein 3
K06593 NECTIN4, PVRL4; poliovirus receptor-related 4
K07836 RAP1B; Ras-related protein Rap-1B
K07860 RAC2; Ras-related C3 botulinum toxin substrate 2
K07861 RAC3; Ras-related C3 botulinum toxin substrate 3
K10351 MYL2; myosin regulatory light chain 2
K12753 MYL5; myosin regulatory light chain 5
K12754 MYL7; myosin regulatory light chain 7
K12755 MYL9; myosin regulatory light chain 9
K12756 MYL10; myosin regulatory light chain 10
K12757 MYL12; myosin regulatory light chain 12
K12758 MYLPF; fast skeletal myosin light chain 2
K16848 IQGAP1; Ras GTPase-activating-like protein IQGAP1
K17705 KRIT1, CCM1; Krev interaction trapped protein 1
K18269 PDCD10, CCM3; programmed cell death protein 10
K20644 ARHGAP29; Rho GTPase-activating protein 29
K23605 SMAD3; mothers against decapentaplegic homolog 3
K23612 WASL; neural Wiskott-Aldrich syndrome protein
K26416 CCM2; cerebral cavernous malformations 2
K26417 RASIP1; Ras-interacting protein 1
K26418 RADIL; Ras-associating and dilute domain-containing protein
Reference Authors Nelson WJ, Nusse R.
Title Convergence of Wnt, beta-catenin, and cadherin pathways.
Journal Reference Authors Potter E, Bergwitz C, Brabant G.
Title The cadherin-catenin system: implications for growth and differentiation of endocrine tissues.
Journal Reference Authors Beavon IR.
Title The E-cadherin-catenin complex in tumour metastasis: structure, function and regulation.
Journal Reference Authors Reynolds AB, Roczniak-Ferguson A.
Title Emerging roles for p120-catenin in cell adhesion and cancer.
Journal 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 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 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 Reference Authors Ciruna B, Rossant J.
Title FGF signaling regulates mesoderm cell fate specification and morphogenetic movement at the primitive streak.
Journal 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 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 Reference Authors Nakanishi H, Takai Y.
Title Roles of nectins in cell adhesion, migration and polarization.
Journal 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 Related ko04060 Cytokine-cytokine receptor interaction
ko04810 Regulation of actin cytoskeleton
