Switch #: SWTI000357

Switch type: Avidity-sensing

Description:
Phosphorylation of two 14-3-3-binding motifs in Kinase suppressor of Ras 1 (Ksr1) by Q03141 induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (Ywhab). This interaction prevents Kinase suppressor of Ras 1 (Ksr1) to localise to the membrane where it is involved in activation of MAP kinases by Q99N57 in response to growth factors.

Participants:
(1) 14-3-3 protein beta/alpha (Ywhab)
(2) Kinase suppressor of Ras 1 (Ksr1)

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 Ywhab - Ywhab

Interfaces
(1) 14-3-3 protein in 14-3-3 protein beta/alpha (Ywhab)
(2) 14-3-3 protein _(5-238) in 14-3-3 protein beta/alpha (Ywhab)

2Interaction #2 Ksr1 - Interaction #1 Ywhab - Ywhab

Requires Interaction #1 Ywhab - Ywhab

Interfaces
(3) LIG_14-3-3_3 motif (₂₉₄RSKSHE₂₉₉) in Kinase suppressor of Ras 1 (Ksr1)
(4) Interaction #1 Ywhab - Ywhab

Interaction Regulation
PTM-dependent Induction (Phosphorylation of S₂₉₇ on Kinase suppressor of Ras 1 (Ksr1)) of the Kinase suppressor of Ras 1 (Ksr1) LIG_14-3-3_3 motif - 14-3-3 protein interaction

Regulatory Enzymes for switch
Modifying enzymes for residue: S₂₉₇: MAP/microtubule affinity-regulating kinase 3 (Mark3)

2Interaction #3 Ksr1 - Interaction #1 Ywhab - Ywhab

Requires Interaction #1 Ywhab - Ywhab

Interfaces
(5) LIG_14-3-3_3 motif (₃₈₉RTESVP₃₉₄) in Kinase suppressor of Ras 1 (Ksr1)
(6) Interaction #1 Ywhab - Ywhab

Interaction Regulation
PTM-dependent Induction (Phosphorylation of S₃₉₂ on Kinase suppressor of Ras 1 (Ksr1)) of the Kinase suppressor of Ras 1 (Ksr1) LIG_14-3-3_3 motif - 14-3-3 protein interaction

Regulatory Enzymes for switch
Modifying enzymes for residue: S₃₉₂: MAP/microtubule affinity-regulating kinase 3 (Mark3)

Inferred Regulatory Enzymes for switch
Putative modifying enzymes for residue: S₃₉₂ : Nucleoside diphosphate kinase A (NME1), Mitogen-activated protein kinase kinase kinase 7 (Map3k7).

(1) Identification of constitutive and ras-inducible phosphorylation sites of KSR: implications for 14-3-3 binding, mitogen-activated protein kinase binding, and KSR overexpression.
Cacace et al. Mol. Cell. Biol. (1999)

(2) C-TAK1 regulates Ras signaling by phosphorylating the MAPK scaffold, KSR1.
Müller et al. Mol. Cell (2001)