Switch #:
SWTI000271
Switch type:
Cumulative
Switch subtype:
Rheostatic

Description:
While phosphorylation of Y1069 induces binding, additional phosphorylation of S1070 and S1071 in the TKB-binding motif of Epidermal growth factor receptor (EGFR) gradually lowers its binding affinity for E3 ubiquitin-protein ligase CBL (CBL).

Participants:
(1) Epidermal growth factor receptor (EGFR)
(2) E3 ubiquitin-protein ligase CBL (CBL)

Interactions
Interaction #1 EGFR - CBL

Interfaces
(1) ELM:LIG_TKB motif (1069YSSDPT1074) in Epidermal growth factor receptor (EGFR)
(2) E3 ubiquitin-protein ligase CBL (CBL)

Interaction Regulation
PTM-dependent Inhibition (Phosphorylation of S1070 and S1071 on Epidermal growth factor receptor (EGFR)) of the Epidermal growth factor receptor (EGFR) LIG_TKB motif - E3 ubiquitin-protein ligase CBL (CBL) interaction

Inferred Regulatory Enzymes for switch
Putative modifying enzymes for residue: S1070 : Calcium/calmodulin-dependent protein kinase type II subunit alpha (CAMK2A), Calcium/calmodulin-dependent protein kinase type II subunit alpha (Camk2a). S1071 : Calcium/calmodulin-dependent protein kinase type II subunit alpha (CAMK2A), Calcium/calmodulin-dependent protein kinase type II subunit alpha (Camk2a).

Additional Information
Affinity : pY1069: 1.0 µM, pY1069-pS1070: 25.8 µM, pY1069-pS1070-pS1071: 31.5 µM
Structural information: 3OB2
Context
Switch localisation
Inferred: nucleus


Switch pathways
Inferred: Endocytosis, ErbB 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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