dishevelled

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Dishevelled specific domain
	; Solution structure of the mouse Dvl-1 DEP domain based on the PDB 1fsh coordinates.
Identifiers
Symbol	Dishevelled
Pfam	PF02377
InterPro	IPR003351
PROSITE	PDOC50841
Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

ほつれた

PrepTutorEJDIC

(服装・髪などが)乱れた,ぼさぼさの

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/01/07 14:54:00」(JST)

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Look up dishevelled in Wiktionary, the free dictionary.

Dishevelled (Dsh) is a family of proteins involved in canonical and non-canonical Wnt signalling pathways. Dsh is a cytoplasmic phosphoprotein that acts directly downstream of frizzled receptors.^[1] It takes its name from its initial discovery in flies, where a mutation in the dishevelled gene was observed to cause improper orientation of body and wing hairs.^[2]

Dishevelled plays important roles in both the embryo and the adult, ranging from cellular differentiation and cell polarity to social behavior.^[2]

Members[edit]

There are three human genes that encode dishevelled proteins:^[3]

DVL1
DVL2
DVL3

Overview of signal transduction pathways involved in apoptosis.

References[edit]

^ Penton A, Wodarz A, Nusse R (June 2002). "A mutational analysis of dishevelled in Drosophila defines novel domains in the dishevelled protein as well as novel suppressing alleles of axin". Genetics 161 (2): 747–62. PMC 1462152. PMID 12072470. Cite uses deprecated parameters (help)
^ ^a ^b Wallingford JB, Habas R (October 2005). "The developmental biology of Dishevelled: an enigmatic protein governing cell fate and cell polarity". Development 132 (20): 4421–36. doi:10.1242/dev.02068. PMID 16192308. Cite uses deprecated parameters (help); |accessdate= requires |url= (help)
^ Lee YN, Gao Y, Wang HY (February 2008). "Differential mediation of the Wnt canonical pathway by mammalian Dishevelleds-1, -2, and -3". Cell. Signal. 20 (2): 443–52. doi:10.1016/j.cellsig.2007.11.005. PMC 2233603. PMID 18093802. Cite uses deprecated parameters (help)

External links[edit]

dishevelled proteins at the US National Library of Medicine Medical Subject Headings (MeSH)

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English Journal

Mammalian sterile 20-like kinase 1/2 inhibits the Wnt/β-catenin signalling pathway by directly binding casein kinase 1ε.

Xu F1, Wang YL1, Chang JJ1, Du SC1, Diao L1, Jiang N1, Wang HJ2, Ma D, Zhang J1.Author information 1*Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Institute of Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China.2†Children's Hospital, Fudan University, Shanghai 200032, China.AbstractThe Hippo signalling pathway can suppress the Wnt/β-catenin signalling pathway through the last downstream effectors YAP (Yes-associated protein)/TAZ (tafazzin). MST (mammalian sterile 20-like kinase) 1 functions as the upstream kinase of the Hippo pathway, and CK1ε (casein kinase 1ε) plays roles in the up-stream signal transduction of the Wnt/β-catenin pathway. In the present study, using tandem affinity purification and MS analysis, CK1ε was identified as a novel partner of MST1. Further analysis showed that the interaction between MST1 and CK1ε was mediated by their kinase domains and enhanced by the activation of MST1. To exclude the interference of the phosphorylated YAP/TAZ, the transduction from MST1 to YAP/TAZ was blocked using anti-WW45 shRNA. In the sh-WW45 cells, MST1 still inhibited the Wnt3A-induced phosphorylation of DVL2 (dishevelled 2) and Wnt/β-catenin signalling by disturbing the interaction of DVL2 and CK1ε. The growth-suppressive effect of MST1 in the presence of Wnt3A was effectively relieved by the downstream activation of the Wnt/β-catenin pathway. Moreover, MST2, the close homologue of MST1, also displayed the similar function in suppressing the Wnt/β-catenin pathway. Therefore the results of the present study revealed that, in addition to the phosphorylated YAP/TAZ, the Hippo pathway can suppress the Wnt/β-catenin pathway directly through MST1/2.
The Biochemical journal.Biochem J.2014 Feb 15;458(1):159-69. doi: 10.1042/BJ20130986.
The Hippo signalling pathway can suppress the Wnt/β-catenin signalling pathway through the last downstream effectors YAP (Yes-associated protein)/TAZ (tafazzin). MST (mammalian sterile 20-like kinase) 1 functions as the upstream kinase of the Hippo pathway, and CK1ε (casein kinase 1ε) plays roles
PMID 24180524

β-Arrestin Promotes Wnt-induced Low Density Lipoprotein Receptor-related Protein 6 (Lrp6) Phosphorylation via Increased Membrane Recruitment of Amer1 Protein.

Kríz V, Pospíchalová V, Masek J, Kilander MB, Slavík J, Tanneberger K, Schulte G, Machala M, Kozubík A, Behrens J, Bryja V.Author information From the Faculty of Science, Institute of Experimental Biology, Masaryk University, 611 37 Brno, Czech Republic.Abstractβ-Arrestin is a scaffold protein that regulates signal transduction by seven transmembrane-spanning receptors. Among other functions it is also critically required for Wnt/β-catenin signal transduction. In the present study we provide for the first time a mechanistic basis for the β-arrestin function in Wnt/β-catenin signaling. We demonstrate that β-arrestin is required for efficient Wnt3a-induced Lrp6 phosphorylation, a key event in downstream signaling. β-Arrestin regulates Lrp6 phosphorylation via a novel interaction with phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2)-binding protein Amer1/WTX/Fam123b. Amer1 has been shown very recently to bridge Wnt-induced and Dishevelled-associated PtdIns(4,5)P2 production to the phosphorylation of Lrp6. Using fluorescence recovery after photobleaching we show here that β-arrestin is required for the Wnt3a-induced Amer1 membrane dynamics and downstream signaling. Finally, we show that β-arrestin interacts with PtdIns kinases PI4KIIα and PIP5KIβ. Importantly, cells lacking β-arrestin showed higher steady-state levels of the relevant PtdInsP and were unable to increase levels of these PtdInsP in response to Wnt3a. In summary, our data show that β-arrestins regulate Wnt3a-induced Lrp6 phosphorylation by the regulation of the membrane dynamics of Amer1. We propose that β-arrestins via their scaffolding function facilitate Amer1 interaction with PtdIns(4,5)P2, which is produced locally upon Wnt3a stimulation by β-arrestin- and Dishevelled-associated kinases.
The Journal of biological chemistry.J Biol Chem.2014 Jan 10;289(2):1128-41. doi: 10.1074/jbc.M113.498444. Epub 2013 Nov 21.
β-Arrestin is a scaffold protein that regulates signal transduction by seven transmembrane-spanning receptors. Among other functions it is also critically required for Wnt/β-catenin signal transduction. In the present study we provide for the first time a mechanistic basis for the β-arrestin func
PMID 24265322

Wnt signaling pathway in non-small cell lung cancer.

Stewart DJ.Author information Affiliation of author: Division of Medical Oncology, University of Ottawa, Ottawa, ON, Canada.AbstractWnt/β-catenin alterations are prominent in human malignancies. In non-small cell lung cancer (NSCLC), β-catenin and APC mutations are uncommon, but Wnt signaling is important in NSCLC cell lines, and Wnt inhibition reduces proliferation. Overexpression of Wnt-1, -2, -3, and -5a and of Wnt-pathway components Frizzled-8, Dishevelled, Porcupine, and TCF-4 is common in resected NSCLC and is associated with poor prognosis. Conversely, noncanonical Wnt-7a suppresses NSCLC development and is often downregulated. Although β-catenin is often expressed in NSCLCs, it was paradoxically associated with improved prognosis in some series, possibly because of E-cadherin interactions. Downregulation of Wnt inhibitors (eg, by hypermethylation) is common in NSCLC tumor cell lines and resected samples; may be associated with high stage, dedifferentiation, and poor prognosis; and has been reported for AXIN, sFRPs 1-5, WIF-1, Dkk-1, Dkk-3, HDPR1, RUNX3, APC, CDX2, DACT2, TMEM88, Chibby, NKD1, EMX2, ING4, and miR-487b. AXIN is also destabilized by tankyrases, and GSK3β may be inactivated through phosphorylation by EGFR. Preclinically, restoration of Wnt inhibitor function is associated with reduced Wnt signaling, decreased cell proliferation, and increased apoptosis. Wnt signaling may also augment resistance to cisplatin, docetaxel, and radiotherapy, and Wnt inhibitors may restore sensitivity. Overall, available data indicate that Wnt signaling substantially impacts NSCLC tumorigenesis, prognosis, and resistance to therapy, with loss of Wnt signaling inhibitors by promoter hypermethylation or other mechanisms appearing to be particularly important. Wnt pathway antagonists warrant exploration clinically in NSCLC. Agents blocking selected specific β-catenin interactions and approaches to increase expression of downregulated Wnt inhibitors may be of particular interest.
Journal of the National Cancer Institute.J Natl Cancer Inst.2014 Jan 1;106(1):djt356. doi: 10.1093/jnci/djt356. Epub 2013 Dec 5.
Wnt/β-catenin alterations are prominent in human malignancies. In non-small cell lung cancer (NSCLC), β-catenin and APC mutations are uncommon, but Wnt signaling is important in NSCLC cell lines, and Wnt inhibition reduces proliferation. Overexpression of Wnt-1, -2, -3, and -5a and of Wnt-pathway
PMID 24309006

Japanese Journal

Immunolocalization of Axin2 and p-Smad3 in Developing Rat Molar Germ

Moriguchi Mitsuko,Yamada Marie,Miake Yasuo,Koshika Mayu
Journal of Hard Tissue Biology 21(2), 113-120, 2012
… Factors in the Wnt signaling pathway: Wnt10, Dishevelled (Dvl), and Axin2, and those in the TGF-β signaling pathway: TGF-β receptor 1 (TGF-β-R1), Smad3, and its active type, phosphorylated Smad3 (p-Smad3), showed similar immunoreactions; …
NAID 130004480543

Immunolocalization of the Factors Related to Wnt Signaling Pathway in Developing Rat Molar

Moriguchi Mitsuko,Yamada Marie,Miake Yasuo,Nitta Yukie
Journal of Hard Tissue Biology 20(3), 185-194, 2011
… In the Wnt/β-catenin signaling pathway, Wnt signal is transmitted to glycogen synthase kinase-3β (GSK-3β) through Dishevelled (Dvl), GSK-3β activity is inhibited, β-catenin phosphorylation is inhibited by the inactive-type GSK-3β, and β-catenin is transferred to the nucleus where it interacts with lymphoid enhancing factor (LEF)/T-cell factor (TCF), a transcription factor, which is considered to induce and regulate gene expression. …
NAID 130004722018