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)

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)

Inferred Regulatory Enzymes for switch
Putative modifying enzymes for residue: S₃₇ : GSK-3_group, Glycogen synthase kinase-3 alpha (GSK3A), Glycogen synthase kinase-3 beta (GSK3B), Inhibitor of nuclear factor kappa-B kinase subunit alpha (CHUK), Mitogen-activated protein kinase 8 (MAPK8).

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)

Inferred Regulatory Enzymes for switch
Putative modifying enzymes for residue: S₃₃ : GSK-3_group, Glycogen synthase kinase-3 alpha (GSK3A), Glycogen synthase kinase-3 beta (GSK3B), Inhibitor of nuclear factor kappa-B kinase subunit alpha (CHUK), Mitogen-activated protein kinase 8 (MAPK8). S₃₇ : GSK-3_group, Glycogen synthase kinase-3 alpha (GSK3A), Glycogen synthase kinase-3 beta (GSK3B), Inhibitor of nuclear factor kappa-B kinase subunit alpha (CHUK), Mitogen-activated protein kinase 8 (MAPK8).

Additional Information
Structural information: 1P22

(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)