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Name |
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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.
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Class |
Cellular Processes; Cellular community - eukaryotes
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Pathway map |

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Disease |
H00647 | Ectodermal dysplasia-syndactyly syndrome |
H00801 | Familial thoracic aortic aneurysm and dissection |
H00942 | Rabson-Mendenhall syndrome |
H01023 | Juvenile polyposis syndrome |
H01228 | Insulin-resistant diabetes mellitus with acanthosis nigricans |
H01255 | Juvenile-onset dystonia |
H01274 | Growth delay due to insulin-like growth factor I resistance |
H02474 | Blepharocheilodontic syndrome |
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Other DBs |
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Orthology |
K06081 | poliovirus receptor-related protein 1 |
K06531 | poliovirus receptor-related protein 2 |
K06592 | poliovirus receptor-related protein 3 |
K06593 | poliovirus receptor-related 4 |
K04237 | partitioning defective protein 3 |
K06082 | FERM, RhoGEF and pleckstrin domain protein 2 |
K04393 | cell division control protein 42 |
K04392 | Ras-related C3 botulinum toxin substrate 1 |
K07860 | Ras-related C3 botulinum toxin substrate 2 |
K07861 | Ras-related C3 botulinum toxin substrate 3 |
K23612 | neural Wiskott-Aldrich syndrome protein |
K05747 | Wiskott-Aldrich syndrome protein |
K16848 | Ras GTPase-activating-like protein IQGAP1 |
K05627 | BAI1-associated protein 2 |
K05753 | WAS protein family, member 1 |
K05748 | WAS protein family, member 2 |
K06083 | WAS protein family, member 3 |
K06085 | synovial sarcoma, X breakpoint 2 interacting protein |
K06086 | sorbin and SH3 domain containing protein 1 |
K05701 | tight junction protein 1 |
K05689 | cadherin 1, type 1, E-cadherin |
K05690 | catenin (cadherin-associated protein), delta 1 |
K04513 | Ras homolog gene family, member A |
K03115 | casein kinase II subunit beta |
K04490 | transcription factor 7-like 1 |
K04491 | transcription factor 7-like 2 |
K04492 | lymphoid enhancer-binding factor 1 |
K23605 | mothers against decapentaplegic homolog 3 |
K04501 | mothers against decapentaplegic homolog 4 |
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Reference |
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Authors |
Nelson WJ, Nusse R. |
Title |
Convergence of Wnt, beta-catenin, and cadherin pathways. |
Journal |
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Reference |
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Authors |
Potter E, Bergwitz C, Brabant G. |
Title |
The cadherin-catenin system: implications for growth and differentiation of endocrine tissues. |
Journal |
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Reference |
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Authors |
Beavon IR. |
Title |
The E-cadherin-catenin complex in tumour metastasis: structure, function and regulation. |
Journal |
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Reference |
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Authors |
Reynolds AB, Roczniak-Ferguson A. |
Title |
Emerging roles for p120-catenin in cell adhesion and cancer. |
Journal |
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Reference |
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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 |
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Authors |
Lilien J, Balsamo J, Arregui C, Xu G. |
Title |
Turn-off, drop-out: functional state switching of cadherins. |
Journal |
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Reference |
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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 |
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Reference |
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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. |
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Reference |
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Authors |
Ciruna B, Rossant J. |
Title |
FGF signaling regulates mesoderm cell fate specification and morphogenetic movement at the primitive streak. |
Journal |
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Reference |
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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 |
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Reference |
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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 |
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Reference |
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Authors |
Nakanishi H, Takai Y. |
Title |
Roles of nectins in cell adhesion, migration and polarization. |
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Reference |
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Authors |
Irie K, Shimizu K, Sakisaka T, Ikeda W, Takai Y. |
Title |
Roles and modes of action of nectins in cell-cell adhesion. |
Journal |
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Related pathway |
ko04060 | Cytokine-cytokine receptor interaction |
ko04810 | Regulation of actin cytoskeleton |
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LinkDB |
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