CK1_alpha

Protein CK1_alpha_*

Identifiers
casein kinase 1, alpha 1
HUGO:CSNK1A1, HGNC:2451, ENTREZ:1452, UNIPROT:P48729, GENECARDS:GC05M148854
HUGO:CSNK1A1 HGNC:2451 ENTREZ:1452 UNIPROT:P48729
HUGO:CSNK1A1 HGNC:2451 ENTREZ:1452 UNIPROT:P48729 GENECARDS:CSNK1A1 REACTOME:57867 KEGG:1452 ATLASONC:CSNK1A1ID40168ch5q32 WIKI:CSNK1A1

Maps_Modules
HMC:ACTIVATING_INVASION_AND_METASTASIS
EMT Senescence / EMT_REGULATORS
EMT Senescence / CELL_CELL_ADHESIONS
EMT Senescence / ADHERENS_JUNCTIONS
HMC:RESISTING_CELL_DEATH
Regulated Cell Death / APOPTOSIS
Regulated Cell Death / MOMP_REGULATION
HMC:EVADING_GROWTH_SUPPRESSORS
Survival / WNT_CANONICAL

References
PMID:12051714
Activation of the canonical Wnt signalling pathway results in stabilisation and nuclear translocation of b-catenin.
In the absence of a Wnt signal, b-catenin is phosphorylated at four conserved serine and threonine residues at the N-terminus of the protein, which results in b-catenin ubiquitination and proteasome-dependent degradation.
The phosphorylation of 3 of these residues, Thr41, Ser37, and Ser33, is mediated by glycogen synthase kinase-3 (GSK-3) in a sequential manner, beginning from the C-terminal Thr41.
It has recently been shown that the GSK-3 dependent phosphorylation of b-catenin requiresprior priming through phosphorylation of Ser45
GSK-3b wasfound to be unable to phosphorylate b-catenin at Ser45 in vitro and in intact cells.
In vitro, CK1, but not CK2, phosphorylates Ser45. Ser45 phosphorylation in intact cells is not mediated by CK1e, a known positive regulator of Wnt signalling.
PMID:7641885

CK1_alpha_*@Cytosol

References
em_emtc_emtc_re464( EMT Senescence ):
CSNK1 (casein kinase 1) but not CSNK2 (casein kinase 2) phosphorylates CTNNB1 at S45.
This priming phosphorylation results in subsequent phosphorylation by GSK3B at T41, S37, S33.
CTNNB1 that is phosphorylated at S33 and S37 is ultimately recognized by E3-ligase and targeted for proteasomal destruction.
PMID:7542250
Whereas in the normal cells CTNNB1 (beta-catenin) is found in association with E-cadherin, p120 Cas is not. In the ras-transformed cells, the situation is reversed; tyrosine-phosphorylated p120 Cas, but not tyrosine-phosphorylated CTNNB1, now is detected in E-cadherin complexes.
The tyrosine-phosphorylated CTNNB1 also shows increased detergent solubility, suggesting a decreased association with the actin cytoskeleton.
decreased tyrosine phosphorylation of CTNNB1 is accompanied by increased interaction with both E-cadherin and the detergent insoluble cytoskeletal fraction
PMID:12051714
Activation of the canonical Wnt signalling pathway results in stabilisation and nuclear translocation of b-catenin.
In the absence of a Wnt signal, b-catenin is phosphorylated at four conserved serine and threonine residues at the N-terminus of the protein, which results in b-catenin ubiquitination and proteasome-dependent degradation.
The phosphorylation of 3 of these residues, Thr41, Ser37, and Ser33, is mediated by glycogen synthase kinase-3 (GSK-3) in a sequential manner, beginning from the C-terminal Thr41.
It has recently been shown that the GSK-3 dependent phosphorylation of b-catenin requiresprior priming through phosphorylation of Ser45
GSK-3b wasfound to be unable to phosphorylate b-catenin at Ser45 in vitro and in intact cells.
In vitro, CK1, but not CK2, phosphorylates Ser45. Ser45 phosphorylation in intact cells is not mediated by CK1e, a known positive regulator of Wnt signalling.
PMID:11955436
Wnt regulation of b-catenin degradation is essential for development and carcinogenesis.
b-catenin degradation is initiated upon amino-terminal serine/threonine phosphorylation.
This phosphorylation is believed to be performed by GSK3B in complex with tumor suppressor proteins Axin and adnomatous polyposis coli (APC).
There is another Axin-associated kinase, whose phosphorylation of b-catenin precedes and is required for subsequent GSK-3 phosphorylation of b-catenin.
This priming kinase is casein kinase I -alpha (CSNK1A1).
PMID:11967263
Tyr-216 phosphorylation in GSK3B is required for GSK-mediated down-regulation of b-catenin activity.
PMID:8666229
Xenopus GSK3 functions to destabilize b-catenin and thus decrease the amount of b-catenin available for signaling
em_emtc_emtc_re1008( EMT Senescence ):
PMID:17353278
Phosphorylation of E-cadherin at S846 by casein kinase I decreases its ability to bind to CTNNB1.
em_emtc_emtc_re1012( EMT Senescence ):
PMID:10581160
PMID:17318175
PMID:10421629
Recruitment of CTNNB1 via the degradation complex of APC/AXIN1 is regulated by a series of ordered phosphorylation events.
Phosphorylation of AXIN1 by CSNK1 (casein kinase 1) and GSK3B can increase axin binding to CTNNB1.
PMID:8638126
PMID:11487578
PMID:15327768
AXIN1 also promotes phosphorylation of APC by CSNK1 and GSK3B.
Phosphorylated APC has higher affinity to CTNNB1.
PMID:12554650
Finally, these phosphorylation events allo CTNNB1 to be a more efficient substrate of both CSNK1 (at S45) and the GSK3B (at T41, S33, S37).
The affinity of phosphorylated APC to CTNNB1 is higher than that of phosphorylated AXIN1.
Therefore upon phosphorylation, APC can displace AXIN1 from CTNNB1, allowing AXIN1 to bind another molecule of CTNNB1.

CK1_alpha_*@Cytoplasm

References
s_wca2_re52:( Survival ) PMID:19244247
s_wca1_re39:( Survival ) PMID:21606194
s_wca2_re51:( Survival ) PMID:21152425 PMID:19244247

CK1_alpha_*@Cytoplasm

Maps_Modules
HMC:EVADING_GROWTH_SUPPRESSORS
Survival / WNT_CANONICAL

References
s_wca2_re52:( Survival ) PMID:19244247

Modifications:
In compartment: Cytoplasm

CK1_alpha_*@Cytoplasm
CK1_alpha_*@Cytoplasm

In compartment: Cytosol

CK1_alpha_*@Cytosol

Participates in complexes:
In compartment: Cytoplasm

In compartment: Endosome

Participates in reactions:
As Reactant or Product:

As Catalyser: