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Switch #:
SWTI000296
Switch type:
Specificity
Switch subtype:
Altered binding specificity

Description:
Phosphorylation of Catenin beta-1 (CTNNB1) at T41 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B), which then phosphorylates S37, thereby generating a new docking site for GSK3B. Subsequent phosphorylation of S33 by GSK3B switches the specificity of CTNNB1 to the F-box/WD repeat-containing protein 1A (BTRC), which recruits CTNNB1 to the SCF ubiquitin ligase complex.

Participants:
(1) Catenin beta-1 (CTNNB1)
(2) Glycogen synthase kinase-3 beta (GSK3B)
(3) F-box/WD repeat-containing protein 1A (BTRC)

Interactions
This is a sequential switch. The interactions in this switch take place in a defined order. The order is defined by numbers to the left of each interaction. More than one interaction can occur in each step, these interactions occur independently but are necessary for future step
1Interaction #1 CTNNB1 - GSK3B

Is mutually exclusive with

Interfaces
(1) MOD_GSK3_1 motif (34GIHSGATT41) in Catenin beta-1 (CTNNB1)
(2) Protein kinase domain (56-340) in Glycogen synthase kinase-3 beta (GSK3B)

Interaction Regulation
PTM-dependent Induction (Phosphorylation of T41 on Catenin beta-1 (CTNNB1)) of the Catenin beta-1 (CTNNB1) MOD_GSK3_1 motif - Glycogen synthase kinase-3 beta (GSK3B) Protein kinase domain interaction

2Interaction #2 CTNNB1 - GSK3B

Requires Interaction #1 CTNNB1 - GSK3B
Is mutually exclusive with

Interfaces
(3) MOD_GSK3_1 motif (30YLDSGIHS37) in Catenin beta-1 (CTNNB1)
(4) Protein kinase domain (56-340) in Glycogen synthase kinase-3 beta (GSK3B)

Interaction Regulation
PTM-dependent Induction (Phosphorylation of S37 on Catenin beta-1 (CTNNB1)) of the Catenin beta-1 (CTNNB1) MOD_GSK3_1 motif - Glycogen synthase kinase-3 beta (GSK3B) Protein kinase domain interaction

Regulatory Enzymes for switch
Modifying enzymes for residue: S37: Glycogen synthase kinase-3 beta (GSK3B)


3Interaction #3 CTNNB1 - BTRC

Requires Interaction #2 CTNNB1 - GSK3B
Is mutually exclusive with

Interfaces
(5) DEG_SCF_TRCP1_1 motif (32DSGIHS37) in Catenin beta-1 (CTNNB1)
(6) WD domain, G-beta repeat (297-329) and (333-369) and (373-409) and (416-452) and (456-492) and (496-532) and (545-581) in F-box/WD repeat-containing protein 1A (BTRC)

Interaction Regulation
PTM-dependent Induction (Phosphorylation of S33 and S37 on Catenin beta-1 (CTNNB1)) of the Catenin beta-1 (CTNNB1) DEG_SCF_TRCP1_1 motif - F-box/WD repeat-containing protein 1A (BTRC) WD domain, G-beta repeat interaction

Regulatory Enzymes for switch
Modifying enzymes for residue: S33: Glycogen synthase kinase-3 beta (GSK3B); S37: Glycogen synthase kinase-3 beta (GSK3B)


Additional Information
Structural information: 1P22
Context
References

(1) Structure of a beta-TrCP1-Skp1-beta-catenin complex: destruction motif binding and lysine specificity of the SCF(beta-TrCP1) ubiquitin ligase.
Wu et al. Mol. Cell (2003)

(2) Characterisation of the phosphorylation of beta-catenin at the GSK-3 priming site Ser45.
Hagen et al. Biochem. Biophys. Res. Commun. (2002)

See also

Other switches involving participants
Glycogen synthase kinase-3 beta (GSK3B) - 18 more (view)
Catenin beta-1 (CTNNB1) - 3 more (view)
F-box/WD repeat-containing protein 1A (BTRC) - 17 more (view)

Other switches involving interfaces
Protein kinase domain - 35 more (view)
MOD_GSK3_1 - 18 more (view)
WD domain, G-beta repeat - 36 more (view)
DEG_SCF_TRCP1_1 - 17 more (view)




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