Switches.ELM

Switch #:

SWTI000359

Description:
Phosphorylation of two 14-3-3-binding motifs in Insulin receptor substrate 1 (IRS1) induces high-avidity binding to dimeric 14-3-3 protein epsilon (YWHAE).

Participants:
(1) 14-3-3 protein epsilon (YWHAE)
(2) Insulin receptor substrate 1 (IRS1)

Interactions

This is a sequential switch. The interactions in this switch take place in a defined order. The order is defined by numbers to the left of each interaction. More than one interaction can occur in each step, these interactions occur independently but are necessary for future step

1Interaction #1 YWHAE - YWHAE

Interfaces
(1) 14-3-3 protein in 14-3-3 protein epsilon (YWHAE)
(2) 14-3-3 protein_(4-239) in 14-3-3 protein epsilon (YWHAE)

2Interaction #2 IRS1 - Interaction #1 YWHAE - YWHAE

Requires Interaction #1 YWHAE - YWHAE

Interfaces
(3) LIG_14-3-3_3 motif (₃₇₁HSRSIP₃₇₆) in Insulin receptor substrate 1 (IRS1)
(4) Interaction #1 YWHAE - YWHAE

Interaction Regulation
PTM-dependent Induction (Phosphorylation of S₃₇₄ on Insulin receptor substrate 1 (IRS1)) of the Insulin receptor substrate 1 (IRS1) LIG_14-3-3_3 motif - 14-3-3 protein interaction

2Interaction #3 IRS1 - Interaction #1 YWHAE - YWHAE

Requires Interaction #1 YWHAE - YWHAE

Interfaces
(5) LIG_14-3-3_3 motif (₆₃₈KSVSAP₆₄₃) in Insulin receptor substrate 1 (IRS1)
(6) Interaction #1 YWHAE - YWHAE

Interaction Regulation
PTM-dependent Induction (Phosphorylation of S₆₄₁ on Insulin receptor substrate 1 (IRS1)) of the Insulin receptor substrate 1 (IRS1) LIG_14-3-3_3 motif - 14-3-3 protein interaction

Context

Switch localisation
ELM curated: nucleus, cytosol, internal side of plasma membrane

Inferred: cytosol

Switch pathways

Inferred: PI3K-Akt signaling pathway, Neurotrophin signaling pathway

References

(1) 14-3-3 protein binds to insulin receptor substrate-1, one of the binding sites of which is in the phosphotyrosine binding domain.
Ogihara et al. J. Biol. Chem. (1997)