Switches.ELM

Switch #:

SWTI000274

Switch type:
Cumulative

Switch subtype:
Rheostatic

Description:
While phosphorylation of Y757 in the SH2-binding motif of Amyloid beta A4 protein (APP) induces binding to Growth factor receptor-bound protein 2 (GRB2), additional phosphorylation of T743 further increases the strength of the interaction.

Participants:
(1) Amyloid beta A4 protein (APP)
(2) Growth factor receptor-bound protein 2 (GRB2)

Interactions

Interaction #1 APP - GRB2

Interfaces
(1) LIG_SH2_GRB2 motif (₇₅₇YENP₇₆₀) in Amyloid beta A4 protein (APP)
(2) SH2 domain_(60-135) in Growth factor receptor-bound protein 2 (GRB2)

Interaction Regulation
PTM-dependent Enhancement (Phosphorylation of Y₇₅₇ and T₇₄₃ on Amyloid beta A4 protein (APP)) of the Amyloid beta A4 protein (APP) LIG_SH2_GRB2 motif - Growth factor receptor-bound protein 2 (GRB2) SH2 domain interaction

Inferred Regulatory Enzymes for switch
Putative modifying enzymes for residue: T₇₄₃ : Glycogen synthase kinase-3 beta (GSK3B), Cyclin-dependent kinase 1 (CDK1). Y₇₅₇ : Tyrosine-protein kinase Fyn (FYN).

Additional Information
Affinity : T743-Y757: no binding µM, T743-pY757: 0.00257 µM, pT743-pY757:0.000413 µM

Context

Switch localisation
ELM curated: cytosol

References

(1) The interactome of the amyloid beta precursor protein family members is shaped by phosphorylation of their intracellular domains.
Tamayev et al. Mol Neurodegener (2009)