KEGG   PATHWAY: shr04520
shr04520                    Pathway                                

Adherens junction - Sarcophilus harrisii (Tasmanian devil)
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.
Cellular Processes; Cellular community - eukaryotes
Pathway map
shr04520  Adherens junction

Other DBs
GO: 0005912
Sarcophilus harrisii (Tasmanian devil) [GN:shr]
100914634  NECTIN1; nectin-1 isoform X1 [KO:K06081]
100918796  NECTIN2; nectin-2 [KO:K06531]
100917500  nectin-2 [KO:K06531]
100930424  NECTIN3; nectin-3 [KO:K06592]
100921171  NECTIN4; nectin-4 isoform X1 [KO:K06593]
100914747  PARD3; partitioning defective 3 homolog isoform X1 [KO:K04237]
100926529  SRC; proto-oncogene tyrosine-protein kinase Src isoform X3 [KO:K05704] [EC:]
100926827  FARP2; FERM, ARHGEF and pleckstrin domain-containing protein 2 isoform X1 [KO:K06082]
100918370  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
100919657  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
100932383  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
100924669  RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861]
100926155  WASL; neural Wiskott-Aldrich syndrome protein [KO:K23612]
100934222  WAS; wiskott-Aldrich syndrome protein [KO:K05747]
100933251  IQGAP1; ras GTPase-activating-like protein IQGAP1 [KO:K16848]
100929838  BAIAP2; brain-specific angiogenesis inhibitor 1-associated protein 2 isoform X1 [KO:K05627]
100921263  WASF1; wiskott-Aldrich syndrome protein family member 1 isoform X1 [KO:K05753]
100927851  WASF2; wiskott-Aldrich syndrome protein family member 2 [KO:K05748]
100924737  WASF3; wiskott-Aldrich syndrome protein family member 3 isoform X2 [KO:K06083]
100934823  LOW QUALITY PROTEIN: wiskott-Aldrich syndrome protein family member 3-like [KO:K06083]
100934446  AFDN; afadin isoform X1 [KO:K05702]
100929318  LMO7; LIM domain only protein 7 isoform X1 [KO:K06084]
100933315  SSX2IP; afadin- and alpha-actinin-binding protein isoform X1 [KO:K06085]
105750865  afadin- and alpha-actinin-binding protein B isoform X1 [KO:K06085]
100914931  SORBS1; sorbin and SH3 domain-containing protein 1 isoform X1 [KO:K06086]
100917501  ACTN4; alpha-actinin-4 isoform X1 [KO:K05699]
100924961  ACTN1; alpha-actinin-1 isoform X1 [KO:K05699]
100918576  VCL; vinculin isoform X1 [KO:K05700]
100924427  TJP1; tight junction protein ZO-1 isoform X1 [KO:K05701]
100920258  CDH1; cadherin-1 [KO:K05689]
100932295  CTNND1; catenin delta-1 isoform X1 [KO:K05690]
100930636  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
100930828  catenin alpha-1 [KO:K05691]
100925228  CTNNA2; catenin alpha-2 isoform X1 [KO:K05691]
100921282  CTNNA3; catenin alpha-3 isoform X1 [KO:K05691]
100928302  ACTG1; actin, cytoplasmic 2 [KO:K05692]
100919051  ACTB; actin, cytoplasmic 1 [KO:K05692]
100921931  RHOA; transforming protein RhoA [KO:K04513]
100915295  ACP1; low molecular weight phosphotyrosine protein phosphatase isoform X1 [KO:K14394] [EC:]
100927395  PTPRM; receptor-type tyrosine-protein phosphatase mu isoform X1 [KO:K05693] [EC:]
100921448  PTPRB; receptor-type tyrosine-protein phosphatase beta isoform X2 [KO:K05694] [EC:]
116421513  PTPN1; tyrosine-protein phosphatase non-receptor type 1 [KO:K05696] [EC:]
100916661  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X2 [KO:K05697] [EC:]
100919624  PTPRJ; receptor-type tyrosine-protein phosphatase eta isoform X1 [KO:K05698] [EC:]
100919559  CSNK2A1; casein kinase II subunit alpha isoform X1 [KO:K03097] [EC:]
100917554  CSNK2A2; casein kinase II subunit alpha' isoform X1 [KO:K03097] [EC:]
100922225  CSNK2B; casein kinase II subunit beta isoform X2 [KO:K03115]
100930141  TCF7; transcription factor 7 isoform X1 [KO:K02620]
100922609  TCF7L1; transcription factor 7-like 1 [KO:K04490]
100922675  TCF7L2; transcription factor 7-like 2 isoform X11 [KO:K04491]
100934638  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
100916673  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:]
100929204  INSR; insulin receptor isoform X1 [KO:K04527] [EC:]
100917007  MET; hepatocyte growth factor receptor [KO:K05099] [EC:]
100914017  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:]
100914727  ERBB2; receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:]
100914347  FGFR1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:]
100913836  FER; tyrosine-protein kinase Fer isoform X1 [KO:K08889] [EC:]
100923088  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:]
116420608  YES1; tyrosine-protein kinase Yes [KO:K05705] [EC:]
100934330  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:]
100913231  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:]
100913837  SNAI2; zinc finger protein SNAI2 [KO:K05706]
100922085  SNAI1; zinc finger protein SNAI1 [KO:K05707]
100913844  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:]
100913352  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:]
100923201  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
100923569  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
100921187  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:]
100926283  CREBBP; CREB-binding protein isoform X2 [KO:K04498] [EC:]
100920997  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:]
100928564  NLK; serine/threonine-protein kinase NLK [KO:K04468] [EC:]
Nelson WJ, Nusse R.
Convergence of Wnt, beta-catenin, and cadherin pathways.
Science 303:1483-7 (2004)
Potter E, Bergwitz C, Brabant G.
The cadherin-catenin system: implications for growth and differentiation of endocrine tissues.
Endocr Rev 20:207-39 (1999)
Beavon IR.
The E-cadherin-catenin complex in tumour metastasis: structure, function and regulation.
Eur J Cancer 36:1607-20 (2000)
Reynolds AB, Roczniak-Ferguson A.
Emerging roles for p120-catenin in cell adhesion and cancer.
Oncogene 23:7947-56 (2004)
Angst BD, Marcozzi C, Magee AI.
The cadherin superfamily: diversity in form and function.
J Cell Sci 114:629-41 (2001)
Lilien J, Balsamo J, Arregui C, Xu G.
Turn-off, drop-out: functional state switching of cadherins.
Dev Dyn 224:18-29 (2002)
Piedra J, Miravet S, Castano J, Palmer HG, Heisterkamp N, Garcia de Herreros A, Dunach M.
p120 Catenin-associated Fer and Fyn tyrosine kinases regulate beta-catenin Tyr-142 phosphorylation and beta-catenin-alpha-catenin Interaction.
Mol Cell Biol 23:2287-97 (2003)
Conacci-Sorrell M, Simcha I, Ben-Yedidia T, Blechman J, Savagner P, Ben-Ze'ev A.
Autoregulation of E-cadherin expression by cadherin-cadherin interactions: the roles of beta-catenin signaling, Slug, and MAPK.
J Cell Biol 163:847-57 (2003)
Ciruna B, Rossant J.
FGF signaling regulates mesoderm cell fate specification and morphogenetic movement at the primitive streak.
Dev Cell 1:37-49 (2001)
Peinado H, Quintanilla M, Cano A.
Transforming growth factor beta-1 induces snail transcription factor in epithelial cell lines: mechanisms for epithelial mesenchymal transitions.
J Biol Chem 278:21113-23 (2003)
Labbe E, Letamendia A, Attisano L.
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.
Proc Natl Acad Sci U S A 97:8358-63 (2000)
Nakanishi H, Takai Y.
Roles of nectins in cell adhesion, migration and polarization.
Biol Chem 385:885-92 (2004)
Irie K, Shimizu K, Sakisaka T, Ikeda W, Takai Y.
Roles and modes of action of nectins in cell-cell adhesion.
Semin Cell Dev Biol 15:643-56 (2004)
shr04010  MAPK signaling pathway
shr04060  Cytokine-cytokine receptor interaction
shr04310  Wnt signaling pathway
shr04350  TGF-beta signaling pathway
shr04530  Tight junction
shr04810  Regulation of actin cytoskeleton
KO pathway

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