Search results for YWHAB

Showing 15 results out of 32

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Types

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Protein (1 results from a total of 1)

Identifier: R-HSA-48888
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: YWHAB: P31946

Interactor (1 results from a total of 1)

Identifier: P31946-2
Species: Homo sapiens
Primary external reference: UniProt: P31946-2

Complex (5 results from a total of 13)

Identifier: R-HSA-2028645
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-2028630
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-5672861
Species: Homo sapiens
Compartment: lysosomal membrane
Identifier: R-HSA-6802615
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-6802616
Species: Homo sapiens
Compartment: plasma membrane

Reaction (5 results from a total of 14)

Identifier: R-HSA-5672951
Species: Homo sapiens
Compartment: cytosol
In quiescent cells, RAF is maintained in a closed state in which the N-terminal regulatory region sterically blocks the catalytic region (Cutler et al, 1998; Tran et al, 2003; Terai et al, 2005; Tran et al, 2005; reviewed in Udell et al, 2011). This closed state is mediated in part by the intramolecular binding of YWHAB/14-3-3 dimers to two phosphorylated serine residues (S259 and S621 in RAF1, S214 and S582 in ARAF and S365 and S729 in BRAF) (Ory et al, 2003; Jaumot et al, 2001; Fischer et al, 2009; reviewed in Udell et al, 2011).

Identifier: R-HSA-5672824
Species: Homo sapiens
Compartment: lysosomal membrane, cytosol
AKT1S1 (PRAS40) phosphorylation by AKT at Thr246, or at Ser183 by mTORC1, leads to the binding of YWHAB (14-3-3 beta) (Zhang et al. 2002, Kovacina et al. 2003, Oshiro et al. 2007). As AKT1S1 suppresses mTORC1 phosphorylation of physiological substrates S6K1 and 4E-BP1 (Oshiro et al. 2007) binding of YWHAB is proposed to relieve this inhibition (Wang et al. 2012).
Identifier: R-HSA-5672958
Species: Homo sapiens
Compartment: cytosol
Dephosphorylation of KSR1 S406 by PP2A promotes the dissociation of 14-3-3 from this site, exposing both the CR1 region that is required for membrane localization of KSR1 and the MAPK-binding FxFP motif (Ory et al, 2003; Muller et al, 2001; reviewed in Raabe and Raap, 2003).
Identifier: R-HSA-5672960
Species: Homo sapiens
Compartment: cytosol
Dephosphorylation of S259 (S365/S214) by PP2A promotes the transient dissociation of 14-3-3 dimers from this site (Ory et al, 2003; Jaumot et al, 2001; Rommel et al, 1996; reviewed in Raabe and Raap, 2003; Matallanas et al, 2011). In the case of RAF1, displacement of 14-3-3 has also been shown to be promoted by a direct interaction between RAF1 and the cell cycle protein prohibitin (PHB; Rajalingam et al, 2005; reviewed in Rajalingam and Rudel, 2005; Chowdhury et al, 2014).
Identifier: R-HSA-5672954
Species: Homo sapiens
Compartment: cytosol
MARK3-mediated phosphorylation of S311 and particularly S406 promotes the binding of 14-3-3 dimers, sequestering KSR1 in the cytosol in quiescent cells (Cacace et al, 1999; Muller et al, 2000; Muller et al, 2001; reviewed in Raabe and Raap, 2003). Mutation of S406 abrogates 14-3-3 binding and results in constitutive plasma membrane localization of KSR1 (Muller et al, 2001).

Set (1 results from a total of 1)

Identifier: R-HSA-9614573
Species: Homo sapiens
Compartment: cytosol

Pathway (2 results from a total of 2)

Identifier: R-HSA-9660537
Species: Homo sapiens
A complex of MRAS, SHOC2 and the phosphatase PP1 contributes to the activation of RAF proteins by removing an inhibitory phosphorylation that mediates binding to 14-3-3 (also known as YWHAB) proteins (Rodriguez-Viciano et al, 2006; Young et al, 2013;reviewed in Simanshu et al, 2017; Lavoie and Therrien, 2015). Activating and inactivating mutations in each of the components of this dephosphorylating complex have been identified in RASopathies as well as at low frequency in some cancers (Cordeddu et al, 2009; Hannig et al, 2014; Gripp et al, 2016; Higgin et al, 2017; Motta et al, 2016; Motta et al, 2019a,b).
Identifier: R-HSA-2028269
Species: Homo sapiens
Compartment: cytosol
Human Hippo signaling is a network of reactions that regulates cell proliferation and apoptosis, centered on a three-step kinase cascade. The cascade was discovered by analysis of Drosophila mutations that lead to tissue overgrowth, and human homologues of its components have since been identified and characterized at a molecular level. Data from studies of mice carrying knockout mutant alleles of the genes as well as from studies of somatic mutations in these genes in human tumors are consistent with the conclusion that in mammals, as in flies, the Hippo cascade is required for normal regulation of cell proliferation and defects in the pathway are associated with cell overgrowth and tumorigenesis (Oh and Irvine 2010; Pan 2010; Zhao et al. 2010). This group of reactions is also notable for its abundance of protein:protein interactions mediated by WW domains and PPxY sequence motifs (Sudol and Harvey 2010).

There are two human homologues of each of the three Drosophila kinases, whose functions are well conserved: expression of human proteins rescues fly mutants. The two members of each pair of human homologues have biochemically indistinguishable functions. Autophosphorylated STK3 (MST2) and STK4 (MST1) (homologues of Drosophila Hippo) catalyze the phosphorylation and activation of LATS1 and LATS2 (homologues of Drosophila Warts) and of the accessory proteins MOB1A and MOB1B (homologues of Drosophila Mats). LATS1 and LATS2 in turn catalyze the phosphorylation of the transcriptional co-activators YAP1 and WWTR1 (TAZ) (homologues of Drosophila Yorkie).

In their unphosphorylated states, YAP1 and WWTR1 freely enter the nucleus and function as transcriptional co-activators. In their phosphorylated states, however, YAP1 and WWTR1 are instead bound by 14-3-3 proteins, YWHAB and YWHAE respectively, and sequestered in the cytosol.

Several accessory proteins are required for the three-step kinase cascade to function. STK3 (MST2) and STK4 (MST1) each form a complex with SAV1 (homologue of Drosophila Salvador), and LATS1 and LATS2 form complexes with MOB1A and MOB1B (homologues of Drosophila Mats).

In Drosophila a complex of three proteins, Kibra, Expanded, and Merlin, can trigger the Hippo cascade. A human homologue of Kibra, WWC1, has been identified and indirect evidence suggests that it can regulate the human Hippo pathway (Xiao et al. 2011). A molecular mechanism for this interaction has not yet been worked out and the molecular steps that trigger the Hippo kinase cascade in humans are unknown.

Four additional processes related to human Hippo signaling, although incompletely characterized, have been described in sufficient detail to allow their annotation. All are of physiological interest as they are likely to be parts of mechanisms by which Hippo signaling is modulated or functionally linked to other signaling processes. First, the caspase 3 protease cleaves STK3 (MST2) and STK4 (MST1), releasing inhibitory carboxyterminal domains in each case, leading to increased kinase activity and YAP1 / TAZ phosphorylation (Lee et al. 2001). Second, cytosolic AMOT (angiomotin) proteins can bind YAP1 and WWTR1 (TAZ) in their unphosphorylated states, a process that may provide a Hippo-independent mechanism to down-regulate the activities of these proteins (Chan et al. 2011). Third, WWTR1 (TAZ) and YAP1 bind ZO-1 and 2 proteins (Remue et al. 2010; Oka et al. 2010). Fourth, phosphorylated WWTR1 (TAZ) binds and sequesters DVL2, providing a molecular link between Hippo and Wnt signaling (Varelas et al. 2010).

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