KEGG   PATHWAY: mlx04310
Entry
mlx04310                    Pathway                                
Name
Wnt signaling pathway - Mirounga leonina (Southern elephant seal)
Description
Wnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, in many different species and organs. There are at least three different Wnt pathways: the canonical pathway, the planar cell polarity (PCP) pathway and the Wnt/Ca2+ pathway. In the canonical Wnt pathway, the major effect of Wnt ligand binding to its receptor is the stabilization of cytoplasmic beta-catenin through inhibition of the bea-catenin degradation complex. Beta-catenin is then free to enter the nucleus and activate Wnt-regulated genes through its interaction with TCF (T-cell factor) family transcription factors and concomitant recruitment of coactivators. Planar cell polarity (PCP) signaling leads to the activation of the small GTPases RHOA (RAS homologue gene-family member A) and RAC1, which activate the stress kinase JNK (Jun N-terminal kinase) and ROCK (RHO-associated coiled-coil-containing protein kinase 1) and leads to remodelling of the cytoskeleton and changes in cell adhesion and motility. WNT-Ca2+ signalling is mediated through G proteins and phospholipases and leads to transient increases in cytoplasmic free calcium that subsequently activate the kinase PKC (protein kinase C) and CAMKII (calcium calmodulin mediated kinase II) and the phosphatase calcineurin.
Class
Environmental Information Processing; Signal transduction
Pathway map
mlx04310  Wnt signaling pathway
mlx04310

Other DBs
GO: 0016055
Organism
Mirounga leonina (Southern elephant seal) [GN:mlx]
Gene
118009997  PORCN; protein-serine O-palmitoleoyltransferase porcupine [KO:K00181] [EC:2.3.1.250]
118008496  WNT1; proto-oncogene Wnt-1 [KO:K03209]
118018995  WNT2B; protein Wnt-2b [KO:K00182]
118021014  WNT2; protein Wnt-2 [KO:K00182]
118026858  WNT3A; protein Wnt-3a [KO:K00312]
118027173  WNT3; proto-oncogene Wnt-3 [KO:K00312]
118019912  WNT4; protein Wnt-4 [KO:K00408]
118025802  WNT5B; protein Wnt-5b isoform X1 [KO:K00444]
118005025  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
118011751  WNT6; protein Wnt-6 [KO:K00445]
118005134  WNT7A; protein Wnt-7a [KO:K00572]
117998566  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
118017183  WNT8A; protein Wnt-8a [KO:K00714]
118024994  WNT8B; protein Wnt-8b [KO:K00714]
118026884  WNT9A; protein Wnt-9a [KO:K01064]
118027171  WNT9B; protein Wnt-9b [KO:K01064]
118008893  WNT10B; protein Wnt-10b [KO:K01357]
118011750  WNT10A; protein Wnt-10a [KO:K01357]
118004067  WNT11; protein Wnt-11 [KO:K01384]
118021382  WNT16; protein Wnt-16 isoform X1 [KO:K01558]
117999054  CER1; cerberus [KO:K01645]
118024398  NOTUM; palmitoleoyl-protein carboxylesterase NOTUM [KO:K19882] [EC:3.1.1.98]
118008617  WIF1; wnt inhibitory factor 1 [KO:K01691]
118025101  SOST; sclerostin [KO:K16834]
118027074  DKK2; dickkopf-related protein 2 [KO:K02165]
118012979  DKK1; dickkopf-related protein 1 [KO:K02165]
118009919  DKK4; dickkopf-related protein 4 [KO:K02165]
118025213  SERPINF1; pigment epithelium-derived factor [KO:K19614]
118009931  SFRP1; secreted frizzled-related protein 1 [KO:K02166]
118022226  SFRP2; secreted frizzled-related protein 2 [KO:K02176]
118012252  FRZB; secreted frizzled-related protein 3 [KO:K25481]
118020605  SFRP4; secreted frizzled-related protein 4 [KO:K02185]
118024632  SFRP5; secreted frizzled-related protein 5 [KO:K02222]
118019671  RSPO1; R-spondin-1 [KO:K19471]
118015121  RSPO2; R-spondin-2 [KO:K23097]
118000719  RSPO3; R-spondin-3 [KO:K23098]
118011045  RSPO4; R-spondin-4 [KO:K23099]
118015714  LGR4; leucine-rich repeat-containing G-protein coupled receptor 4 [KO:K04309]
118008565  LGR5; leucine-rich repeat-containing G-protein coupled receptor 5 [KO:K04308]
118013809  LGR6; leucine-rich repeat-containing G-protein coupled receptor 6 [KO:K08399]
118024704  RNF43; E3 ubiquitin-protein ligase RNF43 [KO:K15694] [EC:2.3.2.27]
118018621  ZNRF3; E3 ubiquitin-protein ligase ZNRF3 isoform X1 [KO:K16273] [EC:2.3.2.27]
118012141  FZD7; frizzled-7 [KO:K02432]
118020735  FZD1; frizzled-1 [KO:K02432]
118024980  FZD2; frizzled-2 isoform X1 [KO:K02235]
118022125  FZD3; frizzled-3 [KO:K02329]
118003939  FZD4; frizzled-4 [KO:K02354]
118026631  FZD8; frizzled-8 [KO:K02375]
118012097  FZD5; frizzled-5 [KO:K02375]
118015096  FZD6; frizzled-6 [KO:K02376]
118018686  FZD10; frizzled-10 [KO:K02842]
117999200  FZD9; frizzled-9 [KO:K02842]
118016153  LRP5; low-density lipoprotein receptor-related protein 5 [KO:K03068]
118025656  LRP6; low-density lipoprotein receptor-related protein 6 isoform X1 [KO:K03068]
117998441  BAMBI; BMP and activin membrane-bound inhibitor homolog [KO:K10162]
118016442  APCDD1; protein APCDD1 [KO:K25812]
118024106  APCDD1L; LOW QUALITY PROTEIN: protein APCDD1-like [KO:K25812]
117998682  casein kinase I isoform X1 [KO:K08960] [EC:2.7.11.1]
118002374  CCDC88C; protein Daple [KO:K25811]
117999990  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
118020123  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
118006887  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
118024369  FRAT1; proto-oncogene FRAT1 [KO:K03069]
118024374  FRAT2; GSK-3-binding protein FRAT2 [KO:K03069]
118023729  CSNK2A2; casein kinase II subunit alpha' [KO:K03097] [EC:2.7.11.1]
118011365  CSNK2A1; casein kinase II subunit alpha isoform X1 [KO:K03097] [EC:2.7.11.1]
118027334  CSNK2B; casein kinase II subunit beta isoform X1 [KO:K03115]
118023798  NKD1; protein naked cuticle homolog 1 [KO:K03213]
118006193  NKD2; protein naked cuticle homolog 2 [KO:K03213]
118027014  CXXC4; CXXC-type zinc finger protein 4 [KO:K03344]
118006914  SENP2; sentrin-specific protease 2 isoform X1 [KO:K03345] [EC:3.4.22.68]
118007057  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
118002288  CTNNB1; catenin beta-1 [KO:K02105]
118021650  AXIN1; axin-1 isoform X1 [KO:K02157]
118024344  AXIN2; axin-2 isoform X1 [KO:K04385]
118017527  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
118005119  APC2; adenomatous polyposis coli protein 2 [KO:K02085]
118006658  casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
118006792  casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
118016638  TCF7; transcription factor 7 isoform X1 [KO:K02620]
118007920  TCF7L1; transcription factor 7-like 1 isoform X1 [KO:K04490]
118026323  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
118027079  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
118025108  LZTS2; leucine zipper putative tumor suppressor 2 isoform X1 [KO:K26471]
118020026  CTNNBIP1; beta-catenin-interacting protein 1 [KO:K04493]
117998673  CBY1; protein chibby homolog 1 isoform X1 [KO:K23402]
118003631  CHD8; chromodomain-helicase-DNA-binding protein 8 isoform X1 [KO:K04494] [EC:5.6.2.-]
118017485  MCC; colorectal mutant cancer protein isoform X1 [KO:K26734]
118022084  CCAR2; cell cycle and apoptosis regulator protein 2 isoform X1 [KO:K25816]
118017855  NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
118018619  NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
118014826  SOX17; transcription factor SOX-17 [KO:K04495]
118010805  CTBP1; C-terminal-binding protein 1 isoform X1 [KO:K04496] [EC:1.1.1.428]
117997501  CTBP2; C-terminal-binding protein 2 isoform X1 [KO:K04496] [EC:1.1.1.428]
118023859  TLE7; LOW QUALITY PROTEIN: transducin-like enhancer protein 7 [KO:K04497]
118003711  TLE3; transducin-like enhancer protein 3 isoform X1 [KO:K04497]
118026260  TLE4; transducin-like enhancer protein 4 isoform X1 [KO:K04497]
118027164  TLE1; transducin-like enhancer protein 1 isoform X1 [KO:K04497]
118005517  TLE2; transducin-like enhancer protein 2 isoform X1 [KO:K04497]
118005854  TLE6; transducin-like enhancer protein 6 [KO:K04497]
118006282  CTNND2; catenin delta-2 isoform X1 [KO:K23491]
117998639  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
118021774  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
118005002  RUVBL1; ruvB-like 1 [KO:K04499] [EC:5.6.2.4]
118004627  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
118003430  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
118001330  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
118025301  NLK; serine/threonine-protein kinase NLK [KO:K04468] [EC:2.7.11.24]
118015212  MYC; myc proto-oncogene protein [KO:K04377]
118019356  JUN; transcription factor AP-1 [KO:K04448]
118016074  FOSL1; fos-related antigen 1 [KO:K04502]
118016166  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
118025766  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
118001139  CCND3; G1/S-specific cyclin-D3 [KO:K10152]
118015231  CCN4; CCN family member 4 [KO:K22471]
118001574  PPARD; peroxisome proliferator-activated receptor delta isoform X1 [KO:K04504]
118013151  MMP7; matrilysin isoform X1 [KO:K01397] [EC:3.4.24.23]
118002427  PSEN1; presenilin-1 isoform X1 [KO:K04505] [EC:3.4.23.-]
118005070  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
118019227  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
118000034  TP53; cellular tumor antigen p53 [KO:K04451]
118023813  SIAH1; E3 ubiquitin-protein ligase SIAH1 isoform X1 [KO:K04506] [EC:2.3.2.27]
118026710  E3 ubiquitin-protein ligase SIAH1A-like [KO:K04506] [EC:2.3.2.27]
118022104  calcyclin-binding protein-like [KO:K04507]
118006294  calcyclin-binding protein-like [KO:K04507]
118014345  calcyclin-binding protein-like [KO:K04507]
118014441  CACYBP; calcyclin-binding protein [KO:K04507]
118016639  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
118026695  TBL1X; F-box-like/WD repeat-containing protein TBL1X [KO:K04508]
118006472  TBL1XR1; F-box-like/WD repeat-containing protein TBL1XR1 isoform X1 [KO:K04508]
118016673  FBXW11; F-box/WD repeat-containing protein 11 isoform X1 [KO:K03362]
118025164  BTRC; F-box/WD repeat-containing protein 1A isoform X1 [KO:K03362]
118021218  CUL1; cullin-1 [KO:K03347]
117998640  RBX1; E3 ubiquitin-protein ligase RBX1 isoform X1 [KO:K03868] [EC:2.3.2.32]
118013141  GPC4; glypican-4 [KO:K08110]
118018958  ROR1; inactive tyrosine-protein kinase transmembrane receptor ROR1 [KO:K05122] [EC:2.7.10.1]
118026362  ROR2; tyrosine-protein kinase transmembrane receptor ROR2 [KO:K05123] [EC:2.7.10.1]
118003888  RYK; tyrosine-protein kinase RYK isoform X1 [KO:K05128] [EC:2.7.10.1]
118000487  VANGL1; vang-like protein 1 [KO:K04510]
118013985  VANGL2; vang-like protein 2 [KO:K04510]
118001138  PRICKLE4; prickle-like protein 4 isoform X1 [KO:K04511]
118008947  PRICKLE1; prickle-like protein 1 [KO:K04511]
118010371  PRICKLE3; prickle planar cell polarity protein 3 isoform X1 [KO:K04511]
118005691  PRICKLE2; prickle-like protein 2 [KO:K04511]
118017886  INVS; inversin isoform X1 [KO:K19626]
118001227  DAAM2; disheveled-associated activator of morphogenesis 2 isoform X1 [KO:K04512]
118002137  DAAM1; disheveled-associated activator of morphogenesis 1 [KO:K04512]
118005670  RHOA; transforming protein RhoA [KO:K04513]
118007595  ROCK2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.1]
118018155  LOW QUALITY PROTEIN: ras-related C3 botulinum toxin substrate 1-like [KO:K04392]
117999338  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
117998715  RAC2; ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860]
118024428  RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861]
118022776  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
118010368  mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
118026506  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
118015997  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
118003092  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
118011244  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
118011247  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
118024497  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
118027107  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
118006598  calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
118006728  calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
118021697  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
118022080  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
118027044  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
118021556  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
118008037  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
118017875  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
118024347  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
117999123  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
117997993  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
118004651  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
118023976  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
118023644  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
118003690  NFATC4; nuclear factor of activated T-cells, cytoplasmic 4 isoform X1 [KO:K17334]
Compound
C00076  Calcium cation
Reference
  Authors
Hatsell S, Rowlands T, Hiremath M, Cowin P.
  Title
Beta-catenin and Tcfs in mammary development and cancer.
  Journal
J Mammary Gland Biol Neoplasia 8:145-58 (2003)
DOI:10.1023/A:1025944723047
Reference
  Authors
Yang Y.
  Title
Wnts and wing: Wnt signaling in vertebrate limb development and musculoskeletal morphogenesis.
  Journal
Birth Defects Res Part C Embryo Today 69:305-17 (2003)
DOI:10.1002/bdrc.10026
Reference
  Authors
Kalderon D.
  Title
Similarities between the Hedgehog and Wnt signaling pathways.
  Journal
Trends Cell Biol 12:523-31 (2002)
DOI:10.1016/S0962-8924(02)02388-7
Reference
  Authors
Nusse R.
  Title
Wnts and Hedgehogs: lipid-modified proteins and similarities in signaling mechanisms at the cell surface.
  Journal
Development 130:5297-305 (2003)
DOI:10.1242/dev.00821
Reference
  Authors
Jope RS, Johnson GV.
  Title
The glamour and gloom of glycogen synthase kinase-3.
  Journal
Trends Biochem Sci 29:95-102 (2004)
DOI:10.1016/j.tibs.2003.12.004
Reference
  Authors
Veeman MT, Axelrod JD, Moon RT.
  Title
A second canon. Functions and mechanisms of beta-catenin-independent Wnt signaling.
  Journal
Dev Cell 5:367-77 (2003)
DOI:10.1016/S1534-5807(03)00266-1
Reference
  Authors
Sun TQ, Lu B, Feng JJ, Reinhard C, Jan YN, Fantl WJ, Williams LT.
  Title
PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt signalling.
  Journal
Nat Cell Biol 3:628-36 (2001)
DOI:10.1038/35083016
Reference
  Authors
Saito-Diaz K, Chen TW, Wang X, Thorne CA, Wallace HA, Page-McCaw A, Lee E
  Title
The way Wnt works: Components and mechanism.
  Journal
Growth Factors 31:1-31 (2013)
DOI:10.3109/08977194.2012.752737
Reference
  Authors
Carethers JM
  Title
Intersection of transforming growth factor-beta and Wnt signaling pathways in colorectal cancer and metastasis.
  Journal
Gastroenterology 137:33-6 (2009)
DOI:10.1053/j.gastro.2009.05.011
Reference
  Authors
Lin Z, Gao C, Ning Y, He X, Wu W, Chen YG
  Title
The pseudoreceptor BMP and activin membrane-bound inhibitor positively modulates Wnt/beta-catenin signaling.
  Journal
J Biol Chem 283:33053-8 (2008)
DOI:10.1074/jbc.M804039200
Reference
  Authors
Niehrs C
  Title
The complex world of WNT receptor signalling.
  Journal
Nat Rev Mol Cell Biol 13:767-79 (2012)
DOI:10.1038/nrm3470
Reference
  Authors
Abou Ziki MD, Mani A
  Title
Wnt signaling, a novel pathway regulating blood pressure? State of the art review.
  Journal
Atherosclerosis 262:171-178 (2017)
DOI:10.1016/j.atherosclerosis.2017.05.001
Reference
  Authors
He Y, Ki H, Kim H, Kim K
  Title
delta-Catenin interacts with LEF-1 and negatively regulates its transcriptional activity.
  Journal
Cell Biol Int 39:954-61 (2015)
DOI:10.1002/cbin.10465
Reference
  Authors
Esaki N, Enomoto A, Takagishi M, Mizutani Y, Iida T, Ushida K, Shiraki Y, Mii S, Takahashi M
  Title
The Daple-CK1epsilon complex regulates Dvl2 phosphorylation and canonical Wnt signaling.
  Journal
Biochem Biophys Res Commun 532:406-413 (2020)
DOI:10.1016/j.bbrc.2020.08.066
Reference
  Authors
Yiew NKH, Chatterjee TK, Tang YL, Pellenberg R, Stansfield BK, Bagi Z, Fulton DJ, Stepp DW, Chen W, Patel V, Kamath VM, Litwin SE, Hui DY, Rudich SM, Kim HW, Weintraub NL
  Title
A novel role for the Wnt inhibitor APCDD1 in adipocyte differentiation: Implications for diet-induced obesity.
  Journal
J Biol Chem 292:6312-6324 (2017)
DOI:10.1074/jbc.M116.758078
Related
pathway
mlx04010  MAPK signaling pathway
mlx04110  Cell cycle
mlx04115  p53 signaling pathway
mlx04120  Ubiquitin mediated proteolysis
mlx04350  TGF-beta signaling pathway
mlx04510  Focal adhesion
mlx04520  Adherens junction
mlx05010  Alzheimer disease
KO pathway
ko04310   
LinkDB

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