| Entry |
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| Name |
Adherens junction
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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; Cell communication
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| Pathway map |
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| Disease |
| Piebaldism | | Nephrotic syndrome and focal segmental glomerulosclerosis | | Ectodermal dysplasia-syndactyly syndrome (EDSS) | | Leprechaunism | | Waardenburg syndrome (WS) | | Loeys-Dietz syndrome (LDS) | | Familial thoracic aortic aneurysm and dissection (TAAD) | | Rabson-Mendenhall syndrome | | Pilomatricoma | | Juvenile polyposis syndrome | | Trigonocephaly | | Insulin-resistant diabetes mellitus with acanthosis nigricans (IRAN) | | Juvenile-onset dystonia | | Growth delay due to insulin-like growth factor I resistance |
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| Other DBs |
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| Reference |
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| Authors |
Nelson WJ, Nusse R. |
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| Title |
Convergence of Wnt, beta-catenin, and cadherin pathways. |
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| Journal |
Science 303:1483-7 (2004) |
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| Reference |
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| Authors |
Potter E, Bergwitz C, Brabant G. |
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| Title |
The cadherin-catenin system: implications for growth and differentiation of endocrine tissues. |
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| Journal |
Endocr Rev 20:207-39 (1999) |
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| Reference |
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| Authors |
Beavon IR. |
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| Title |
The E-cadherin-catenin complex in tumour metastasis: structure, function and regulation. |
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| Journal |
Eur J Cancer 36:1607-20 (2000) |
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| Reference |
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| Authors |
Reynolds AB, Roczniak-Ferguson A. |
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| Title |
Emerging roles for p120-catenin in cell adhesion and cancer. |
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| Journal |
Oncogene 23:7947-56 (2004) |
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| Reference |
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| Authors |
Angst BD, Marcozzi C, Magee AI. |
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| Title |
The cadherin superfamily: diversity in form and function. |
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| Journal |
J Cell Sci 114:629-41 (2001) |
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| Reference |
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| Authors |
Lilien J, Balsamo J, Arregui C, Xu G. |
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| Title |
Turn-off, drop-out: functional state switching of cadherins. |
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| Journal |
Dev Dyn 224:18-29 (2002) |
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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. |
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| Title |
p120 Catenin-associated Fer and Fyn tyrosine kinases regulate beta-catenin Tyr-142 phosphorylation and beta-catenin-alpha-catenin Interaction. |
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| Journal |
Mol Cell Biol 23:2287-97 (2003) |
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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. |
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| Title |
Autoregulation of E-cadherin expression by cadherin-cadherin interactions: the roles of beta-catenin signaling, Slug, and MAPK. |
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| Journal |
J Cell Biol 163:847-57 (2003) |
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| Reference |
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| Authors |
Ciruna B, Rossant J. |
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| Title |
FGF signaling regulates mesoderm cell fate specification and morphogenetic movement at the primitive streak. |
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| Journal |
Dev Cell 1:37-49 (2001) |
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| Reference |
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| Authors |
Peinado H, Quintanilla M, Cano A. |
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| Title |
Transforming growth factor beta-1 induces snail transcription factor in epithelial cell lines: mechanisms for epithelial mesenchymal transitions. |
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| Journal |
J Biol Chem 278:21113-23 (2003) |
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| Reference |
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| Authors |
Labbe E, Letamendia A, Attisano L. |
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| 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. |
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| Journal |
Proc Natl Acad Sci U S A 97:8358-63 (2000) |
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| Reference |
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| Authors |
Nakanishi H, Takai Y. |
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| Title |
Roles of nectins in cell adhesion, migration and polarization. |
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| Journal |
Biol Chem 385:885-92 (2004) |
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| Reference |
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| Authors |
Irie K, Shimizu K, Sakisaka T, Ikeda W, Takai Y. |
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| Title |
Roles and modes of action of nectins in cell-cell adhesion. |
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| Journal |
Semin Cell Dev Biol 15:643-56 (2004) |
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| KO pathway |
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