Back بروتين دبيلو.أن.تي Arabic Wnt-signalni put BS Wnt signalizace Czech Wnt-Signalweg German Vía de señalización WNT Spanish Wnt signaalirada Estonian Voie de signalisation Wnt French Vía de sinalización Wnt Galician Wnt proteini Croatian Via di segnalazione di Wnt Italian

Wnt signaling pathway

In cellular biology, the Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt, pronounced "wint", is a portmanteau created from the names Wingless and Int-1.[1] Wnt signaling pathways use either nearby cell-cell communication (paracrine) or same-cell communication (autocrine). They are highly evolutionarily conserved in animals, which means they are similar across animal species from fruit flies to humans.[2][3]

Three Wnt signaling pathways have been characterized: the canonical Wnt pathway, the noncanonical planar cell polarity pathway, and the noncanonical Wnt/calcium pathway. All three pathways are activated by the binding of a Wnt-protein ligand to a Frizzled family receptor, which passes the biological signal to the Dishevelled protein inside the cell. The canonical Wnt pathway leads to regulation of gene transcription, and is thought to be negatively regulated in part by the SPATS1 gene.[4] The noncanonical planar cell polarity pathway regulates the cytoskeleton that is responsible for the shape of the cell. The noncanonical Wnt/calcium pathway regulates calcium inside the cell.

Wnt signaling was first identified for its role in carcinogenesis, then for its function in embryonic development. The embryonic processes it controls include body axis patterning, cell fate specification, cell proliferation and cell migration. These processes are necessary for proper formation of important tissues including bone, heart and muscle. Its role in embryonic development was discovered when genetic mutations in Wnt pathway proteins produced abnormal fruit fly embryos. Later research found that the genes responsible for these abnormalities also influenced breast cancer development in mice. Wnt signaling also controls tissue regeneration in adult bone marrow, skin and intestine.[5]

This pathway's clinical importance was demonstrated by mutations that lead to various diseases, including breast and prostate cancer, glioblastoma, type II diabetes and others.[6][7] In recent years, researchers reported first successful use of Wnt pathway inhibitors in mouse models of disease.[8]

  1. ^ Nusse R, Brown A, Papkoff J, Scambler P, Shackleford G, McMahon A, et al. (January 1991). "A new nomenclature for int-1 and related genes: the Wnt gene family". Cell. 64 (2): 231. doi:10.1016/0092-8674(91)90633-a. PMID 1846319. S2CID 3189574.
  2. ^ Cite error: The named reference doi10.1016/0092-8674(92)90630-U was invoked but never defined (see the help page).
  3. ^ Cite error: The named reference Nusse was invoked but never defined (see the help page).
  4. ^ Zhang H, Zhang H, Zhang Y, Ng SS, Ren F, Wang Y, Duan Y, Chen L, Zhai Y, Guo Q, Chang Z (November 2010). "Dishevelled-DEP domain interacting protein (DDIP) inhibits Wnt signaling by promoting TCF4 degradation and disrupting the TCF4/beta-catenin complex". Cellular Signalling. 22 (11): 1753–60. doi:10.1016/j.cellsig.2010.06.016. PMID 20603214.
  5. ^ Goessling W, North TE, Loewer S, Lord AM, Lee S, Stoick-Cooper CL, Weidinger G, Puder M, Daley GQ, Moon RT, Zon LI (March 2009). "Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration". Cell. 136 (6): 1136–47. doi:10.1016/j.cell.2009.01.015. PMC 2692708. PMID 19303855.
  6. ^ Logan CY, Nusse R (2004). "The Wnt signaling pathway in development and disease". Annual Review of Cell and Developmental Biology. 20: 781–810. CiteSeerX 10.1.1.322.311. doi:10.1146/annurev.cellbio.20.010403.113126. PMID 15473860.
  7. ^ Cite error: The named reference Komiya was invoked but never defined (see the help page).
  8. ^ Zimmerli D, Hausmann G, Cantù C, Basler K (December 2017). "Pharmacological interventions in the Wnt pathway: inhibition of Wnt secretion versus disrupting the protein-protein interfaces of nuclear factors". British Journal of Pharmacology. 174 (24): 4600–4610. doi:10.1111/bph.13864. PMC 5727313. PMID 28521071.

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