Switch #:
SWTI000272
Switch type:
Cumulative
Switch subtype:
Rheostatic

Description:
While phosphorylation of Y55 induces binding, additional phosphorylation of T56 in the TKB-binding motif of Protein sprouty homolog 2 (SPRY2) lowers its binding affinity for E3 ubiquitin-protein ligase CBL (CBL).

Participants:
(1) Protein sprouty homolog 2 (SPRY2)
(2) E3 ubiquitin-protein ligase CBL (CBL)

Interactions
Interaction #1 SPRY2 - CBL

Interfaces
(1) ELM:LIG_TKB motif (55YTEGPT60) in Protein sprouty homolog 2 (SPRY2)
(2) E3 ubiquitin-protein ligase CBL (CBL)

Interaction Regulation
PTM-dependent Inhibition (Phosphorylation of T56 on Protein sprouty homolog 2 (SPRY2)) of the Protein sprouty homolog 2 (SPRY2) LIG_TKB motif - E3 ubiquitin-protein ligase CBL (CBL) interaction

Additional Information
Affinity : pY55-T56: 0.31 µM, pY55-pT56: 3.83 µM
Structural information: 3OB1
Context
Switch localisation
Inferred: plasma membrane, cytosol


Switch pathways
Inferred: Jak-STAT signaling pathway
References

(1) Additional serine/threonine phosphorylation reduces binding affinity but preserves interface topography of substrate proteins to the c-Cbl TKB domain.
Sun et al. PLoS ONE (2010)




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