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Switch #:
SWTI000292
Switch type:
Specificity
Switch subtype:
Altered binding specificity

Description:
Phosphorylation of Y757 in APP (Amyloid beta A4 protein (APP)) switches its specificity from PTB domain containing proteins, like Amyloid beta A4 precursor protein-binding family B member 1 (APBB1), which is involved in trafficking and processing of APP, to SH2 domain containing proteins, such as Growth factor receptor-bound protein 2 (GRB2).

Participants:
(1) Amyloid beta A4 protein (APP)
(2) Amyloid beta A4 precursor protein-binding family B member 1 (APBB1)
(3) Growth factor receptor-bound protein 2 (GRB2)

Interactions
Interaction #2 APP - GRB2

Is mutually exclusive with Interaction #1 APP - APBB1

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

Interaction Regulation
PTM-dependent Induction (Phosphorylation of Y757 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: Y757 : Tyrosine-protein kinase Fyn (FYN).

Context
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)

(2) Phosphorylation of a tyrosine in the amyloid-beta protein precursor intracellular domain inhibits Fe65 binding and signaling.
Zhou et al. J. Alzheimers Dis. (2009)

See also

Other switches involving participants
Amyloid beta A4 protein (APP) - 2 more (view)
Amyloid beta A4 precursor protein-binding family B member 1 (APBB1) - 1 more (view)
Growth factor receptor-bound protein 2 (GRB2) - 12 more (view)

Other switches involving interfaces
SH2 domain - 140 more (view)
Phosphotyrosine interaction domain (PTB/PID) - 14 more (view)
LIG_SH2_GRB2 - 6 more (view)
LIG_PTB_Apo_2 - 3 more (view)




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