Switch #: SWTI000691

Switch type: Specificity

Switch subtype: Altered binding specificity

Description:
Phosphorylation of Yorkie homolog (YAP1) at S381 by Serine/threonine-protein kinase LATS1 (LATS1) (a key regulator of the Hippo Pathway) primes the sequence for phosphorylation by Casein kinase I isoform epsilon (CSNK1E) at S384 and S387. This targets YAP1 to the SCF ubiqutin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks is YAP1 for subsequent degradation by the proteasomal system. N.B. Serine/threonine-protein kinase LATS2 (LATS2) can replace LATS1 and Casein kinase I isoform delta (CSNK1D) can replace CSNK1E

Participants:
(1) Isoform YAP1-2alpha of Yorkie homolog (YAP1)
(2) Serine/threonine-protein kinase LATS1 (LATS1)
(3) Casein kinase I isoform epsilon (CSNK1E)
(4) F-box/WD repeat-containing protein 1A (BTRC)

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 YAP1 - LATS1

Interfaces
(1) MOD_LATS_1 motif (₃₇₆HSRDEST₃₈₂) in Isoform YAP1-2alpha of Yorkie homolog (YAP1)
(2) Protein kinase domain _(705-1010) in Serine/threonine-protein kinase LATS1 (LATS1)

Interaction Regulation
PTM-dependent Induction (Phosphorylation of S₃₈₁ on Isoform YAP1-2alpha of Yorkie homolog (YAP1)) of the Isoform YAP1-2alpha of Yorkie homolog (YAP1) MOD_LATS_1 motif - Serine/threonine-protein kinase LATS1 (LATS1) Protein kinase domain interaction

2Interaction #2 YAP1 - CSNK1E

Interfaces
(3) MOD_CK1_1 motif (₃₈₁STDSGLS₃₈₇) in Isoform YAP1-2alpha of Yorkie homolog (YAP1)
(4) Protein kinase domain _(9-280) in Casein kinase I isoform epsilon (CSNK1E)

Interaction Regulation
PTM-dependent Induction (Phosphorylation of S₃₈₄ on Isoform YAP1-2alpha of Yorkie homolog (YAP1)) of the Isoform YAP1-2alpha of Yorkie homolog (YAP1) MOD_CK1_1 motif - Casein kinase I isoform epsilon (CSNK1E) Protein kinase domain interaction

3Interaction #3 YAP1 - CSNK1E

Interfaces
(5) MOD_CK1_1 motif (₃₈₄SGLSMSS₃₉₀) in Isoform YAP1-2alpha of Yorkie homolog (YAP1)
(6) Protein kinase domain _(9-280) in Casein kinase I isoform epsilon (CSNK1E)

Interaction Regulation
PTM-dependent Induction (Phosphorylation of S₃₈₇ on Isoform YAP1-2alpha of Yorkie homolog (YAP1)) of the Isoform YAP1-2alpha of Yorkie homolog (YAP1) MOD_CK1_1 motif - Casein kinase I isoform epsilon (CSNK1E) Protein kinase domain interaction

4Interaction #4 YAP1 - BTRC

Interfaces
(7) ELM:DEG_SCF_TRCP1_2 motif (₃₈₃DSGLS₃₈₇) in Isoform YAP1-2alpha of Yorkie homolog (YAP1)
(8) WD domain, G-beta repeat _(301-590) in F-box/WD repeat-containing protein 1A (BTRC)

Interaction Regulation
PTM-dependent Induction (Phosphorylation of S₃₈₄ and S₃₈₇ on Isoform YAP1-2alpha of Yorkie homolog (YAP1)) of the Isoform YAP1-2alpha of Yorkie homolog (YAP1) DEG_SCF_TRCP1_2 motif - F-box/WD repeat-containing protein 1A (BTRC) WD domain, G-beta repeat interaction

(1) A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCF(beta-TRCP).
Zhao et al. Genes Dev. (2010)

Other switches involving participants
F-box/WD repeat-containing protein 1A (BTRC) - 17 more (view)

Other switches involving interfaces
Protein kinase domain - 35 more (view)
WD domain, G-beta repeat - 36 more (view)
ELM:DEG_SCF_TRCP1_2 - 2 more (view)