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Ca2+ pathway
Stable Identifier
R-HSA-4086398
Type
Pathway
Species
Homo sapiens
Compartment
plasma membrane
,
cytosol
ReviewStatus
5/5
Locations in the PathwayBrowser
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Signal Transduction (Homo sapiens)
Signaling by WNT (Homo sapiens)
Beta-catenin independent WNT signaling (Homo sapiens)
Ca2+ pathway (Homo sapiens)
General
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A number of so called non-canonical WNT ligands have been shown to promote intracellular calcium release upon FZD binding. This beta-catenin-independent WNT pathway acts through heterotrimeric G proteins and promotes calcium release through phophoinositol signaling and activation of phosphodiesterase (PDE). Downstream effectors include the calcium/calmodulin-dependent kinase II (CaMK2) and PKC (reviewed in De, 2011). The WNT Ca2+ pathway is important in dorsoventral polarity, convergent extension and organ formation in vertebrates and also has roles in negatively regulating 'canonical' beta-catenin-dependent transcription. Non-canonical WNT Ca2+ signaling is also implicated in inflammatory response and cancer (reviewed in Kohn and Moon, 2005; Sugimura and Li, 2010).
Literature References
PubMed ID
Title
Journal
Year
21181886
Noncanonical Wnt signaling in vertebrate development, stem cells, and diseases
Li, L
,
Sugimura, R
Birth Defects Res. C Embryo Today
2010
16099039
Wnt and calcium signaling: beta-catenin-independent pathways
Moon, RT
,
Kohn, AD
Cell Calcium
2005
21903638
Wnt/Ca2+ signaling pathway: a brief overview
De, A
Acta Biochim. Biophys. Sin. (Shanghai)
2011
Participants
Events
WNT5A and WNT11 bind FZD receptors to initiate Ca2+ signaling
(Homo sapiens)
FZD recruits trimeric G-proteins
(Homo sapiens)
WNT:FZD complex promotes G-protein nucleotide exchange
(Homo sapiens)
G-protein subunits dissociate from WNT:FZD complex
(Homo sapiens)
Gbeta:gamma activation of PLC beta
(Homo sapiens)
PLC beta-mediated PIP2 hydrolysis
(Homo sapiens)
Translocation and activation of PKC alpha in response to WNT signaling
(Homo sapiens)
IP3 binds to the IP3 receptor, opening the endoplasmic reticulum Ca2+ channel
(Homo sapiens)
Activation of Calcineurin
(Homo sapiens)
Calcineurin binds and dephosphorylates NFAT1 in response to WNT/Ca2+ signaling
(Homo sapiens)
Translocation of NFATC1:CaN:CaM to nucleus
(Homo sapiens)
Decreasing cGMP concentration promotes intracellular Ca2+ release in response to WNT
(Homo sapiens)
G alpha t2 binds and activates PDE6
(Homo sapiens)
PDE6 hydrolyses cGMP to GMP
(Homo sapiens)
Active calmodulin binds CAMK2
(Homo sapiens)
PRKG is activated by binding to high levels of cGMP in the absence of WNT signaling
(Homo sapiens)
Autophosphorylation and activation of CAMK2
(Homo sapiens)
Dissociation of CaM and CAMK2 autophosphorylation
(Homo sapiens)
CAMK2 binds MAP3K7
(Homo sapiens)
Activation of MAP3K7 in response to WNT
(Homo sapiens)
Activation of NLK
(Homo sapiens)
NLK translocates to nucleus
(Homo sapiens)
NLK phosphorylates TCF/LEF
(Homo sapiens)
miR-92b binds 3'UTR of NLK mRNA
(Homo sapiens)
NLK mRNA translation controlled by miR-92b
(Homo sapiens)
TCF/LEF:CTNNB1 bind canonical WNT target promoters
(Homo sapiens)
Transcription of canonical WNT targets is negatively regulated by NLK-dependent phosphorylation of TCF/LEF
(Homo sapiens)
Participates
as an event of
Beta-catenin independent WNT signaling (Homo sapiens)
Event Information
Go Biological Process
Wnt signaling pathway, calcium modulating pathway (0007223)
Orthologous Events
Ca2+ pathway (Bos taurus)
Ca2+ pathway (Caenorhabditis elegans)
Ca2+ pathway (Canis familiaris)
Ca2+ pathway (Dictyostelium discoideum)
Ca2+ pathway (Drosophila melanogaster)
Ca2+ pathway (Gallus gallus)
Ca2+ pathway (Mus musculus)
Ca2+ pathway (Plasmodium falciparum)
Ca2+ pathway (Rattus norvegicus)
Ca2+ pathway (Saccharomyces cerevisiae)
Ca2+ pathway (Schizosaccharomyces pombe)
Ca2+ pathway (Sus scrofa)
Ca2+ pathway (Xenopus tropicalis)
Authored
Rothfels, K (2013-08-08)
Reviewed
Kikuchi, A (2013-11-13)
Created
Rothfels, K (2013-08-08)
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