WNT/Beta-katenin sinyal yolunun sitoplazmik biyomolekülleri

DÖNMEZ, HANİFE GÜLER; BEKSAÇ, Mehmet Sinan; DEMİREZEN, Sayeste

WNT/Beta-katenin sinyal yolunun sitoplazmik biyomolekülleri

Hanife Güler DÖNMEZ, (Hacettepe Üniversitesi, Fen Fakültesi, Biyoloji Bölümü, Ankara, Türkiye)

Sayeste DEMİREZEN, (Hacettepe Üniversitesi, Fen Fakültesi, Biyoloji Bölümü, Ankara, Türkiye)

Mehmet Sinan BEKSAÇ (Hacettepe Üniversitesi, Tıp Fakültesi, Kadın Hastalıkları ve Doğum Anabilim Dalı, Ankara, Türkiye)

Dokuz Eylül Üniversitesi Tıp Fakültesi Dergisi

18 5

Yıl: 2011 Cilt: 25 Sayı: 3 Sayfa Aralığı: 189 - 199 Metin Dili: Türkçe İndeks Tarihi: 29-07-2022

WNT/Beta-katenin sinyal yolunun sitoplazmik biyomolekülleri

Öz:

Omurgasızlardan omurgalılara kadar evrimsel olarak oldukça korunan Wnt/β-katenin sinyal yolu hem erken embriyonik gelişimin düzenlenmesinde, hem de erişkin dokularda apoptozis, adipogenez, anjiogenez, sinaps oluşumu gibi olaylarda rol almaktadır. Bununla birlikte bu sinyal yolunda meydana gelen bozuklukların kanser başta olmak üzere birçok ciddi hastalığın etiyolojisinde rolü olduğunun düşünülmesi, son yıllarda bu sinyal yolu ile ilgili araştırmaları oldukça arttırmıştır. Wnt/β-katenin sinyal yolunun bu hastalıklardaki rolünü belirlemeye yönelik çalışmalarda çoğunlukla β- katenin, Axin, Adenomatöz Polipozis Koli (APC) gibi biyomoleküller araştırılmaktadır. Ayrıca, bu biyomoleküller sadece hastalıkların oluşum mekanizmalarının belirlenmesinde değil, bu hastalıkların tedavisinde hedef olarak da kullanılmakta-dırlar. Dolayısıyla Wnt/β-katenin sinyal yolunun en önemli basamağı olan sitoplazmik reaksiyonların ve bu reaksiyonlarda görev alan biyomoleküllerin ortaya konulması sinyal yolunun bütünün tam olarak anlaşılması için oldukça önemlidir. Bu sebeple derlememizde hedef hücre sitoplazmasında görev yapan biyomoleküllerin tartışılması ve bu şekilde sinyal yolunun tam olarak aydınlatılması amaçlanmıştır.

Anahtar Kelime:

Konular: Cerrahi

Cytoplasmic biomolecules of WNT/Beta-catenin signaling pathway

Öz:

Wnt/β-catenin signaling pathway, which is highly evolutionarily conserved from invertebrates to vertebrates, regulates apoptosis, adipogenesis, angiogenesis, synapse formation in adult tissues, and controls embryonic development in the embryo. Researches related to the signal pathway because of its probable role in the etiology of serious diseases such as cancer are quite increased. In the studies, for determining the role of Wnt/β-catenin signaling pathway in these diseases, are mostly investigated biomolecules such as β-catenin, Axin, Adenomatous Polyposis Coli (APC). In addition, these biomolecules are not only used in determining the mechanisms of diseases, but also used as a target for treatment. Thus, determination of the cytoplasmic reactions, which are the most important step of the Wnt/beta-catenin signaling pathway, and biomolecules of these reactions are very important for understanding of fully signaling mechanism. Therefore, discussion of biomolecules in the cytoplasm of target cells and identification of the entire mechanism of the signaling pathway were aimed in our review.

Anahtar Kelime:

Konular: Cerrahi

Belge Türü: Makale Makale Türü: Derleme Erişim Türü: Erişime Açık

1. Kikuchi A, Yamamoto H, Kishida S. Multiplicity of the interactions of Wnt proteins and their receptors. Cell Signal 2007;19:659-671.
2. Rothbächer U, Laurent MN, Deardorff MA, Klein PS, Cho KW, Fraser SE. Dishevelled phosphorylation, subcellular localization and multimerization regulate its role in early embryogenesis. EMBO J 2000;19:1010-1022.
3. Zeng X, Tamai K, Doble B et al. A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation. Nature 2005;438:873-877.
4. Xing Y, Clements WK, Kimelman D, Xu W. Crystal structure of a beta-catenin/axin complex suggests a mechanism for the beta-catenin destruction complex. Genes Dev 2003;17:2753-2764.
5. Wu G, Huang H, Garcia Abreu J, He X. Inhibition of GSK3 phosphorylation of beta-catenin via phosphorylated PPPSPXS motifs of Wnt coreceptor LRP6. PLoS One 2009;4:4926.
6. Kemler R. From cadherins to catenins: cytoplasmic protein interactions and regulation of cell adhesion. Trends Genet 1993;9:317-321.
7. Brembeck FH, Rosário M, Birchmeier W. Balancing cell adhesion and Wnt signaling, the key role of beta-catenin. Curr Opin Genet Dev 2006;16:51-59.
8. Maher MT, Flozak AS, Stocker AM, Chenn A, Gottardi CJ. Activity of the β-catenin phosphodestruction complex at cell-cell contacts is enhanced by cadherin-based adhesion. J Cell Biol 2009;186:219-228.
9. Verheyen EM, Gottardi CJ. Regulation of Wnt/betacatenin signaling by protein kinases. Dev Dyn 2010; 239: 34-44.
10. Aberle H, Bauer A, Stappert J, Kispert A, Kemler R. Beta-catenin is a target for the ubiquitin-proteasome pathway. EMBO J 1997;16:3797-3804.
11. Fahmy OG, Fahmy M. New mutant report. Dros Inf Serv 1959;33:85.
12. Klingensmith J, Nusse R, Perrimon N. The Drosophila segment polarity gene dishevelled encodes a novel protein required for response to the wingless signal. Genes Dev 1994;8:118-130.
13. Lee YN, Gao Y, Wang HY. Differential mediation of the Wnt canonical pathway by mammalian Dishevelleds-1, - 2, and -3. Cell Signal 2008;20:443-452.
14. Tsang M, Lijam N, Yang Y, Beier DR, Wynshaw-Boris A, Sussman DJ. Isolation and characterization of mouse dishevelled-3. Dev Dyn 1996;207:253-262.
15. Pan WJ, Pang SZ, Huang T, Guo HY, Wu D, Li L. Characterization of function of three domains in dishevelled- 1: DEP domain is responsible for membrane translocation of dishevelled-1. Cell Res 2004;14:324-330.
16. Wong HC, Bourdelas A, Krauss A et al. Direct binding of the PDZ domain of Dishevelled to a conserved internal sequence in the C-terminal region of Frizzled. Mol Cell 2003;12:1251-1260.
17. Klimowski LK, Garcia BA, Shabanowitz J, Hunt DF, Virshup DM. Site-specific casein kinase 1epsilon-dependent phosphorylation of Dishevelled modulates beta-catenin signaling. FEBS J 2006;273:4594-4602.
18. Boutros M, Mlodzik M. Dishevelled: at the crossroads of divergent intracellular signaling pathways. Mech Dev 1999; 83:27-37.
19. Cliffe A, Hamada F, Bienz M. A role of Dishevelled in relocating Axin to the plasma membrane during wingless signaling. Curr Biol 2003;13:960-966.
20. Kishida S, Yamamoto H, Hino S, Ikeda S, Kishida M, Kikuchi A. DIX domains of Dvl and axin are necessary for protein interactions and their ability to regulate betacatenin stability. Mol Cell Bio 1999;19:4414-4422.
21. Cadigan KM, Liu YI. Wnt signaling: Complexity at the surface. J Cell Sci 2006;119:395-402.
22. Okino K, Nagai H, Hatta M et al. Up-regulation and overproduction of DVL-1, the human counterpart of the Drosophila dishevelled gene, in cervical squamous cell carcinoma. Oncol Rep 2003;10:1219-1223.
23. Bui TD, Beier DR, Jonssen M et al. cDNA cloning of a human dishevelled DVL-3 gene, mapping to 3q27, and expression in human breast and colon carcinomas. Biochem Biophys Res Commun 1997;239:510-516.
24. Mizutani K, Miyamoto S, Nagahata T, Konishi N, Emi M, Onda M. Upregulation and overexpression of DVL1, the human counterpart of the Drosophila dishevelled gene, in prostate cancer. Tumori 2005;91:546-551.
25. Wei Q, Zhao Y, Yang ZQ et al. Dishevelled family proteins are expressed in non-small cell lung cancer and function differentially on tumor progression. Lung Cancer 2008;62:181-192.
26. Uematsu K, Seki N, Seto T et al. Targeting the Wnt signaling pathway with dishevelled and cisplatin synergistically suppresses mesothelioma cell growth. Anticancer Res 2007;27:4239-4242.
27. Mahindroo N, Punchihewa C, Bail AM, Fujii N. Indole- 2-amide based biochemical antagonist of Dishevelled PDZ domain interaction down-regulates Dishevelleddriven Tcf transcriptional activity. Bioorg Med Chem Lett 2008;18:946-949.
28. Hunter T. Protein kinases and phosphatases: the yin and yang of protein phosphorylation and signaling. Cell 1995;80:225-236.
29. Vielhaber E, Virshup DM. Casein kinase I: from obscurity to center stage. IUBMB Life 2001;51:73-78.
30. Mckay RM, Peters JM, Graff JM. The casein Kinase I family in Wnt signaling. Dev Biol 2001;235:388-396.
31. Peters JM, McKay RM, McKay JP, Graff JM. Casein kinase I transduces Wnt signals. Nature 1999;401:345-350.
32. Knippschild U, Gocht A, Wolff S, Huber N, Löhler J, Stöter M. The casein kinase 1 family: participation in multiple cellular processes in eukaryotes. Cell Signal 2005; 17:675-689.
33. Davidson G, Wu W, Shen J et al. Casein kinase 1γ couples Wnt receptor activation to cytoplasmic signal transduction. Nature 2005;438:867-872.
34. Kishida M., Hino S, Michiue T et al. Synergistic activation of the Wnt signaling pathway by Dvl and casein kinase I>. J Biol Chem 2001;276:33147-33155.
35. Gao ZH, Seeling JM, Hill V, Yochum A, Virshup DM. Casein kinase I phosphorylates and destabilizes the β- catenin degradation complex. Proc Natl Acad Sci 2002;99:1182-1187.
36. Nyati S, Ranga R, Ross BD, Rehemtulla A, Bhojani MS. Molecular imaging of glycogen synthase kinase-3beta and casein kinase-1alpha kinases. Anal Biochem 2010;405: 246-254.
37. Zeng X, Tamai K, Doble B et al. A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation. Nature 2005;438:873-877.
38. Hagen T, Vidal-Puig A. Characterization of the phosphorylation of beta-catenin at the GSK-3 priming site Ser45. Biochem Biophys Res Commun 2002;294:324-328.
39. van Noort M, van de Wetering M, Clevers H. Identification of two novel regulated serines in the N terminus of beta-catenin. Exp Cell Res 2002;276:264-272.
40. Thorne CA, Hanson AJ, Schneider J et al. Small-molecule inhibition of Wnt signaling through activation of casein kinase 1α. Nat Chem Biol 2010;6:829-836.
41. Zeng L, Fagotto F, Zhang T et al. The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation. Cell 1997;90: 181-192.
42. Salahshor S, Woodgett JR. The links between Axin and carcinogenesis. J Clin Pathol 2005;58:225-236.
43. Kikuchi A. Roles of Axin in the Wnt signalling pathway. Cell Signal 1999;11:777-788.
44. Ikeda S, Kishida S, Yamamoto H, Murai H, Koyama S, Kikuchi A. Axin, a negative regulator of the Wnt signal ing pathway, forms a complex with GSK-3beta and betacatenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin. EMBO J 1998;17:1371-1384.
45. Tolwinski NS, Wehrli M, Rives A, Erdeniz N, DiNardo S, Wieschaus E. Wg/Wnt signal can be transmitted through arrow/LRP5,6 and Axin independently of Zw3/Gsk3beta activity. Dev Cell 2003;4:407-418.
46. Mao J, Wang J, Liu B et al. Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway. Mol Cell 2001; 7:801-809.
47. Tamai K, Zeng X, Liu C et al. A mechanism for Wnt Coreceptor Activation. Mol Cell 2004;13:149-156.
48. Willert K, Jones KA. Wnt signaling: is the party in the nucleus? Genes Dev 2006;20:1394-1404.
49. Fumoto K, Kadono M, Izumi N, Kikuchi A. Axin localizes to the centrosome and is involved in microtubule nucleation. EMBO Rep 2009;10:606-613.
50. Choi EJ, Kim SM, Song KJ, Lee JM, Kee SH. Axin1 expression facilitates cell death induced by Aurora kinase inhibition through PARP activation. J Cell Biochem 2011 doi: 10.1002/jcb.23162. [Epub ahead of print]
51. Webster MT, Rozycka M, Sara E et al. Sequence variants of the axin gene in breast, colon, and other cancers: an analysis of mutations that interfere with GSK3 binding. Genes Chromosomes Cancer 2000;28:443-453.
52. Li AF, Hsu PK, Tzao C et al. Reduced axin protein expression is associated with a poor prognosis in patients with squamous cell carcinoma of esophagus. Ann Surg Oncol 2009;16:2486-2493.
53. Yardy GW, Bicknell DC, Wilding JL et al. Mutations in the AXIN1 gene in advanced prostate cancer. Eur Urol 2009;56:486-494.
54. Nikuseva Martić T, Pećina-Slaus N, Kusec V et al. Changes of AXIN-1 and beta-catenin in neuroepithelial brain tumors. Pathol Oncol Res 2010;16:75-79.
55. Satoh S, Daigo Y, Furukawa Y et al. AXIN1 mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of AXIN1. Nat Genet 2000;24:245-250.
56. Doble BW, Woodgett JR. GSK-3: tricks of the trade for a multi-tasking kinase. J Cell Sci 2003;116:1175-1186.
57. Wu D, Pan W. GSK3: a multifaceted kinase in Wnt signaling. Trends Biochem Sci 2010;35:161-168.
58. Yun SI, Yoon HY, Chung YS. Glycogen synthase kinase- 3β regulates etoposide-induced apoptosis via Bcl-2 mediated caspase-3 activation in C3H10T1/2 cells. Apoptosis 2009;14:771-777.
59. Jope RS, Yuskaitis CJ, Beurel E. Glycogen synthase kinase-3 (GSK3): inflammation, diseases, and therapeutics. Neurochem Res 2007;32:577-595.
60. Hofmann C, Dunger N, Schölmerich J, Falk W, Obermeier F. Glycogen synthase kinase 3-β: a master regulator of toll-like receptor-mediated chronic intestinal inflammation. Inflamm Bowel Dis 2010;16:1850-1858.
61. Boonen RA, van Tijn P, Zivkovic D. Wnt signaling in Alzheimer's disease: up or down, that is the question. Ageing Res Rev 2009;8:71-82.
62. Lee J, Kim MS. The role of GSK3 in glucose homeostasis and the development of insulin resistance. Diabetes Res Clin Pract 2007;77:49-57.
63. Jope RS, Roh MS. Glycogen synthase kinase-3 (GSK3) in psychiatric diseases and therapeutic interventions. Curr Drug Targets 2006;7:1421-1434.
64. Bodmer WF, Bailey CJ, Bodmer J et al. Localization of the gene for familial adenomatous polyposis on chromosome 5. Nature 1987;328:614-616.
65. Nakamura Y, Nishisho I, Kinzler KW et al. Mutations of the adenomatous polyposis coli gene in familial polyposis coli patients and sporadic colorectal tumors. Princess Takamatsu Symp 1991;22:285-292.
66. Groden J, Thliveris A, Samowitz W et al. Identification and characterization of the familial adenomatous polyposis coli gene. Cell 1991;66:589-600.
67. Spink KE, Polakis P, Weis WI. Structural basis of the Axin-adenomatous polyposis coli interaction. EMBO J 2000;19:2270-2279.
68. Fearnhead NS, Britton MP, Bodmer WF. The ABC of APC. Hum Mol Genet 2001;10:721-733.
69. Behrens J, Jerchow BA, Würtele M et al. Functional interaction of an axin homolog, conductin, with betacatenin, APC, and GSK3beta. Science 1998;280:596-599.
70. Brocardo M, Henderson BR. APC shuttling to the membrane, nucleus and beyond. Trends Cell Biol 2008;18:587-596.
71. Hanson CA, Miller JR. Non-traditional roles for the Ade nomatous polyposis coli (APC) tumor suppressor protein. Gene 2005;361:1-12.
72. Imura T, Wang X, Noda T et al. Adenomatous polyposis coli is essential for both neuronal differentiation and maintenance of adult neural stem cells in subventricular zone and hippocampus. Stem Cells 2010;28:2053-2064.
73. Miclea RL, Karperien M, Langers AM et al. APC mutations are associated with increased bone mineral density in patients with familial adenomatous polyposis. J Bone Miner Res 2010;25:2348-2356.
74. Segditsas S, Rowan AJ, Howarth K et al. APC and the three-hit hypothesis. Oncogene 2009;28:146-155.
75. Fang DC, Luo YH, Yang SM, Li XA, Ling XL, Fang L. Mutation analysis of APC gene in gastric cancer with microsatellite instability. World J Gastroenterol 2002;8: 787-791.
76. Abraham SC, Wu TT, Hruban RH. Genetic and immunohistochemical analysis of pancreatic acinar cell carcinoma: frequent allelic loss on chromosome 11p and alterations in the APC/beta-catenin pathway. Am J Pathol 2002;160:953-962.
77. Tanwar PS, Zhang L, Roberts DJ, Teixeira JM. Stromal deletion of the APC tumor suppressor in mice triggers development of endometrial cancer. Cancer Res 2011; 71: 1584-1596.
78. Karbova E, Davidson B, Metodiev K, Tropé CG, Nesland JM. Adenomatous polyposis coli (APC) protein expression in primary and metastatic serous ovarian carcinoma. Int J Surg Pathol 2002;10:175-180.
79. Saito T, Oda Y, Sakamoto A et al. APC mutations in synovial sarcoma. J Pathol 2002;196:445-449.
80. Kharaishvili G, Simkova D, Makharoblidze E et al. Wnt signaling in prostate development and carcinogenesis. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2011;155:11-18.
81. Ozawa M, Baribault H, Kemler R. The cytoplasmic domain of the cell adhesion molecule uvomorulin associates with three independent proteins structurally related in different species. EMBO J 1989;8:1711-1717.
82. McCrea PD, Turck CW, Gumbiner B. A homolog of the armadillo protein in Drosophila (plakoglobin) associated with E-cadherin. Science 1991;254:1359-1361.
83. Peifer M, McCrea PD, Green KJ, Wieschaus E, Gumbiner BM. The vertebrate adhesive junction proteins beta-catenin and plakoglobin and the Drosophila segment polarity gene armadillo form a multigene family with similar properties. J Cell Biol 1992;118:681-691.
84. Xu W, Kimelman D. Mechanistic insights from structural studies of beta-catenin and its binding part-ners. J Cell Sci 2007;120:3337-3344.
85. Xing Y, Takemaru K, Liu J et al. Crystal structure of a full-length beta-catenin. Structure 2008;16:478-487.
86. Gamallo C, Palacios J, Moreno G, Calvo de Mora J, Suárez A, Armas A. Beta-catenin expression pattern in stage I and II ovarian carcinomas: relationship with beta-catenin gene mutations, clinicopathological features, and clinical outcome. Am J Pathol 1999;155:527-536.
87. Akisik E, Buğra D, Yamaner S, Dalay N. Analysis of β- catenin alterations in colon tumors: a novel exon 3 mutation. Tumour Biol 2011;32:71-76.
88. Rubinfeld B, Robbins P, El-Gamil M, Albert I, Porfiri E, Polakis P. Stabilization of beta-catenin by genetic defects in melanoma cell lines. Science 1997;275:1790-1792.
89. Fukuchi T, Sakamoto M, Tsuda H, Maruyama K, Nozawa S, Hirohashi S. Beta catenin mutation in carcinoma of the uterine endometrium. Cancer Res 1998; 58:3526-3528.
90. Wong CM, Fan ST, Ng IO. Beta-catenin mutation and overexpression in hepatocellular carcinoma: clinico-pathologic and prognostic significance. Cancer 2001; 92:136-145.
91. Fattet S, Haberler C, Legoix P et al. Beta-catenin status in paediatric medulloblastomas: correlation of immunohistochemical expression with mutational status, genetic profiles, and clinical characteristics. J Pathol 2009; 218: 86-94.
92. Ysebaert L, Chicanne G, Demur C et al. Expression of beta-catenin by acute myeloid leukemia cells predicts enhanced clonogenic capacities and poor prognosis. Leukemia 2006;20:1211-1216.

APA	DÖNMEZ H, DEMİREZEN S, BEKSAÇ M (2011). WNT/Beta-katenin sinyal yolunun sitoplazmik biyomolekülleri. , 189 - 199.
Chicago	DÖNMEZ HANİFE GÜLER,DEMİREZEN Sayeste,BEKSAÇ Mehmet Sinan WNT/Beta-katenin sinyal yolunun sitoplazmik biyomolekülleri. (2011): 189 - 199.
MLA	DÖNMEZ HANİFE GÜLER,DEMİREZEN Sayeste,BEKSAÇ Mehmet Sinan WNT/Beta-katenin sinyal yolunun sitoplazmik biyomolekülleri. , 2011, ss.189 - 199.
AMA	DÖNMEZ H,DEMİREZEN S,BEKSAÇ M WNT/Beta-katenin sinyal yolunun sitoplazmik biyomolekülleri. . 2011; 189 - 199.
Vancouver	DÖNMEZ H,DEMİREZEN S,BEKSAÇ M WNT/Beta-katenin sinyal yolunun sitoplazmik biyomolekülleri. . 2011; 189 - 199.
IEEE	DÖNMEZ H,DEMİREZEN S,BEKSAÇ M "WNT/Beta-katenin sinyal yolunun sitoplazmik biyomolekülleri." , ss.189 - 199, 2011.
ISNAD	DÖNMEZ, HANİFE GÜLER vd. "WNT/Beta-katenin sinyal yolunun sitoplazmik biyomolekülleri". (2011), 189-199.

APA	DÖNMEZ H, DEMİREZEN S, BEKSAÇ M (2011). WNT/Beta-katenin sinyal yolunun sitoplazmik biyomolekülleri. Dokuz Eylül Üniversitesi Tıp Fakültesi Dergisi, 25(3), 189 - 199.
Chicago	DÖNMEZ HANİFE GÜLER,DEMİREZEN Sayeste,BEKSAÇ Mehmet Sinan WNT/Beta-katenin sinyal yolunun sitoplazmik biyomolekülleri. Dokuz Eylül Üniversitesi Tıp Fakültesi Dergisi 25, no.3 (2011): 189 - 199.
MLA	DÖNMEZ HANİFE GÜLER,DEMİREZEN Sayeste,BEKSAÇ Mehmet Sinan WNT/Beta-katenin sinyal yolunun sitoplazmik biyomolekülleri. Dokuz Eylül Üniversitesi Tıp Fakültesi Dergisi, vol.25, no.3, 2011, ss.189 - 199.
AMA	DÖNMEZ H,DEMİREZEN S,BEKSAÇ M WNT/Beta-katenin sinyal yolunun sitoplazmik biyomolekülleri. Dokuz Eylül Üniversitesi Tıp Fakültesi Dergisi. 2011; 25(3): 189 - 199.
Vancouver	DÖNMEZ H,DEMİREZEN S,BEKSAÇ M WNT/Beta-katenin sinyal yolunun sitoplazmik biyomolekülleri. Dokuz Eylül Üniversitesi Tıp Fakültesi Dergisi. 2011; 25(3): 189 - 199.
IEEE	DÖNMEZ H,DEMİREZEN S,BEKSAÇ M "WNT/Beta-katenin sinyal yolunun sitoplazmik biyomolekülleri." Dokuz Eylül Üniversitesi Tıp Fakültesi Dergisi, 25, ss.189 - 199, 2011.
ISNAD	DÖNMEZ, HANİFE GÜLER vd. "WNT/Beta-katenin sinyal yolunun sitoplazmik biyomolekülleri". Dokuz Eylül Üniversitesi Tıp Fakültesi Dergisi 25/3 (2011), 189-199.