Switches.ELM

Switch #:

SWTI000288

Switch type:
Specificity

Switch subtype:
Altered binding specificity

Description:
Phosphorylation of T758 in Integrin beta-2 (ITGB2) switches the specificity of ITGB2 from Filamin-A (FLNA) to 14-3-3 proteins (e.g. 14-3-3 protein zeta/delta (YWHAZ)).

Participants:
(1) Integrin beta-2 (ITGB2)
(2) Filamin-A (FLNA)
(3) 14-3-3 protein zeta/delta (YWHAZ)

Interactions

Interaction #1 ITGB2 - FLNA

Is mutually exclusive with Interaction #2 ITGB2 - YWHAZ

Interfaces
(1) ELM:LIG_Filamin motif (₇₅₃LFKSATTTVMN₇₆₃) in Integrin beta-2 (ITGB2)
(2) Filamin/ABP280 repeat_(2235-2322) in Filamin-A (FLNA)

Interaction Regulation
PTM-dependent Abrogation (Phosphorylation of T₇₅₈ on Integrin beta-2 (ITGB2)) of the Integrin beta-2 (ITGB2) LIG_Filamin motif - Filamin-A (FLNA) Filamin/ABP280 repeat interaction

Inferred Regulatory Enzymes for switch
Putative modifying enzymes for residue: T₇₅₈ : PKC_group, Protein kinase C beta type (PRKCB), Protein kinase C beta type (PRKCB), Protein kinase C alpha type (PRKCA), Protein kinase C delta type (PRKCD), Protein kinase C eta type (PRKCH).

Additional Information
Affinity : T758: 500 µM, pT758: no binding µM
Structural information: 2JF1

Interaction #2 ITGB2 - YWHAZ

Is mutually exclusive with Interaction #1 ITGB2 - FLNA

Interfaces
(3) LIG_14-3-3_3 motif (₇₅₅KSATTT₇₆₀) in Integrin beta-2 (ITGB2)
(4) 14-3-3 protein_(3-236) in 14-3-3 protein zeta/delta (YWHAZ)

Interaction Regulation
PTM-dependent Induction (Phosphorylation of T₇₅₈ on Integrin beta-2 (ITGB2)) of the Integrin beta-2 (ITGB2) LIG_14-3-3_3 motif - 14-3-3 protein zeta/delta (YWHAZ) 14-3-3 protein interaction

Additional Information
Affinity : T758: no binding µM, pT758: 0.261 µM
Structural information: 2V7D

Context

References

(1) Beta2 integrin phosphorylation on Thr758 acts as a molecular switch to regulate 14-3-3 and filamin binding.
Takala et al. Blood (2008)