Biomaterial Database

Dishevelled: The hub of Wnt signaling. 2010

Chan Gao, and Ye-Guang Chen

Tsinghua University, Beijing, China. ygchen@tsinghua.edu.cn

Wnt signaling controls a variety of developmental and homeostatic events. As a key component of Wnt signaling, Dishevelled (Dvl/Dsh) protein relays Wnt signals from receptors to downstream effectors. In the canonical Wnt pathway that depends on the nuclear translocation of beta-catenin, Dvl is recruited by the receptor Frizzled and prevents the constitutive destruction of cytosolic beta-catenin. In the non-canonical Wnt pathways such as Wnt-Frizzled/PCP (planar cell polarity) signaling, Dvl signals via the Daam1-RhoA axis and the Rac1 axis. In addition, Dvl plays important roles in Wnt-GSK3beta-microtubule signaling, Wnt-calcium signaling, Wnt-RYK signaling, Wnt-atypical PKC signaling, etc. Dvl also functions to mediate receptor endocytosis. To fulfill its multifaceted functions, it is not surprising that Dvl associates with various kinds of proteins. Its activity is also modulated dynamically by phosphorylation, ubiquitination and degradation. In this review, we summarize the current understanding of Dvl functions in Wnt signal transduction and its biological functions in mouse development, and also discuss the molecular mechanisms of its actions.

UI	MeSH Term	Description	Entries
D010750	Phosphoproteins		Phosphoprotein
D010766	Phosphorylation	The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.	Phosphorylations
D004705	Endocytosis	Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.	Endocytoses
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000072261	Dishevelled Proteins	A family of proteins that are key components of the WNT SIGNALING PATHWAY, where they function downstream of FRIZZLED RECEPTORS. They contain an N-terminal dishevelled-AXIN PROTEIN (DIX) domain, which mediates oligomerization; a central PDZ DOMAIN which binds to the frizzled receptor; and a C-terminal DEP domain which facilitates binding to the CELL MEMBRANE. Dishevelled proteins have important functions in CELL DIFFERENTIATION and establishing CELL POLARITY.	Dishevelled Protein,Dishevelled-1 Protein,Dishevelled-2 Protein,Dishevelled-3 Protein,Dishevelled 1 Protein,Dishevelled 2 Protein,Dishevelled 3 Protein
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D015398	Signal Transduction	The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.	Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D048868	Adaptor Proteins, Signal Transducing	A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes	Signal Transducing Adaptor Proteins
D051153	Wnt Proteins	Wnt proteins are a large family of secreted glycoproteins that play essential roles in EMBRYONIC AND FETAL DEVELOPMENT, and tissue maintenance. They bind to FRIZZLED RECEPTORS and act as PARACRINE PROTEIN FACTORS to initiate a variety of SIGNAL TRANSDUCTION PATHWAYS. The canonical Wnt signaling pathway stabilizes the transcriptional coactivator BETA CATENIN.	Wingless Type Protein,Wnt Factor,Wnt Protein,Wingless Type Proteins,Wnt Factors,Factor, Wnt,Protein, Wingless Type,Protein, Wnt,Type Protein, Wingless
D055550	Protein Stability	The ability of a protein to retain its structural conformation or its activity when subjected to physical or chemical manipulations.	Protein Stabilities,Stabilities, Protein,Stability, Protein