Switches.ELM

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

Additional Information
Affinity : pY1069: 1.0 µM, pY1069-pS1070: 25.8 µM, pY1069-pS1070-pS1071: 31.5 µM
Structural information: 3OB2

Context

Switch localisation

Switch pathways

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)