VRK2 inhibits mitogen-activated protein kinase signaling and inversely correlates with ErbB2 in human breast cancer

Molecular and Cellular Biology

Volumn 30, Issue 19, 2010, Pages 4687-4697

  Fernández, Isabel F ^a   Blanco, Sandra ^a,d   Lozano, José ^b,c   Lazo, Pedro A ^a  

^a Salamanca Spain   (Spain)

^b UNIVERSITY OF MÁLAGA   (Spain)

^c HOSPITAL UNIVERSITARIO VIRGEN DE LA VICTORIA   (Spain)

^d University of Cambridge   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

B RAF KINASE; CALNEXIN; EPIDERMAL GROWTH FACTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; MITOGEN ACTIVATED PROTEIN KINASE; PROTEIN JIP1; PROTEIN KINASE; PROTEIN KSR1; PROTEIN VRK2; SCAFFOLD PROTEIN; UNCLASSIFIED DRUG;

ARTICLE; BREAST CARCINOMA; CONTROLLED STUDY; DOWN REGULATION; GENE SILENCING; HUMAN; HUMAN CELL; HUMAN TISSUE; NUCLEOTIDE SEQUENCE; ONCOGENE H RAS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; SERUM RESPONSIVE ELEMENT; SIGNAL TRANSDUCTION; TRANSCRIPTION INITIATION;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; BREAST NEOPLASMS; CELL LINE; CELL LINE, TUMOR; EPIDERMAL GROWTH FACTOR; HELA CELLS; HUMANS; IMMUNOBLOTTING; MAP KINASE SIGNALING SYSTEM; MICROSCOPY, CONFOCAL; MITOGEN-ACTIVATED PROTEIN KINASES; MUTATION; PHOSPHORYLATION; PROTEIN BINDING; PROTEIN KINASES; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS B-RAF; RAS PROTEINS; RECEPTOR, ERBB-2; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA INTERFERENCE; TRANSCRIPTION, GENETIC;

EID: 77956686282     PISSN: 02707306     EISSN: 10985549     Source Type: Journal    
DOI: 10.1128/MCB.01581-09     Document Type: Article

References (54)

1. Albanese, C., J. Johnson, G. Watanabe, N. Eklund, D. Vu, A. Arnold, and R. G. Pestell. 1995. Transforming p21ras mutants and c-Ets-2 activate the cyclin D1 promoter through distinguishable regions. J. Biol. Chem. 270:23589-23597.
2. Amado, R. G., M. Wolf, M. Peeters, E. Van Cutsem, S. Siena, D. J. Freeman, T. Juan, R. Sikorski, S. Suggs, R. Radinsky, S. D. Patterson, and D. D. Chang. 2008. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J. Clin. Oncol. 26:1626-1634.
3. Benachenhou, N., S. Guiral, I. Gorska-Flipot, D. Labuda, and D. Sinnett. 1998. High resolution deletion mapping reveals frequent allelic losses at the DNA mismatch repair loci hMLH1 and hMSH3 in non-small cell lung cancer. Int. J. Cancer 77:173-180. (Pubitemid 28287965)
4. Blanco, S., L. Klimcakova, F. M. Vega, and P. A. Lazo. 2006. The subcellular localization of vaccinia-related kinase-2 (VRK2) isoforms determines their different effect on p53 stability in tumour cell lines. FEBS J. 273:2487-2504.
5. Blanco, S., and P. A. Lazo. 2009. Vaccinia-related kinase-2. UCSD-Nature Molecule Page doi:10.1038/mp.a000905.01.
6. Blanco, S., C. Santos, and P. A. Lazo. 2007. Vaccinia-related kinase 2 modulates the stress response to hypoxia mediated by TAK1. Mol. Cell. Biol. 27:7273-7283.
7. Blanco, S., M. Sanz-Garcia, C. R. Santos, and P. A. Lazo. 2008. Modulation of interleukin-1 transcriptional response by the interaction between VRK2 and the JIP1 scaffold protein. PLoS One 3:e1660.
8. Bos, J. L. 1989. ras oncogenes in human cancer: a review. Cancer Res. 49:4682-4689. (Pubitemid 19213607)
9. Burgess, A. W. 2008. EGFR family: structure physiology signalling and therapeutic targets. Growth Factors 26:263-274.
10. Casar, B., I. Arozarena, V. Sanz-Moreno, A. Pinto, L. Agudo-Ibanez, R. Marais, R. E. Lewis, M. T. Berciano, and P. Crespo. 2009. Ras subcellular localization defines extracellular signal-regulated kinase 1 and 2 substrate specificity through distinct utilization of scaffold proteins. Mol. Cell. Biol. 29:1338-1353.
11. Chen, C., R. E. Lewis, and M. A. White. 2008. IMP modulates KSR1-dependent multivalent complex formation to specify ERK1/2 pathway activation and response thresholds. J. Biol. Chem. 283:12789-12796.
12. de Muga, S. V., P. Timpson, L. Cubells, R. Evans, T. E. Hayes, C. Rentero, A. Hegemann, M. Reverter, J. Leschner, A. Pol, F. Tebar, R. J. Daly, C. Enrich, and T. Grewal. 2009. Annexin A6 inhibits Ras signalling in breast cancer cells. Oncogene 28:363-377.
13. Dhanasekaran, D. N., K. Kashef, C. M. Lee, H. Xu, and E. P. Reddy. 2007. Scaffold proteins of MAP-kinase modules. Oncogene 26:3185-3202.
14. Dhillon, A. S., S. Hagan, O. Rath, and W. Kolch. 2007. MAP kinase signalling pathways in cancer. Oncogene 26:3279-3290.
15. Di Cosimo, S., and J. Baselga. 2008. Targeted therapies in breast cancer: where are we now? Eur. J. Cancer 44:2781-2790.
16. Fehrenbacher, N., D. Bar-Sagi, and M. Philips. 2009. Ras/MAPK signaling from endomembranes. Mol. Oncol. 3:297-307.
17. Gorjanacz, M., E. P. Klerkx, V. Galy, R. Santarella, C. Lopez-Iglesias, P. Askjaer, and I. W. Mattaj. 2008. Caenorhabditis elegans BAF-1 and its kinase VRK-1 participate directly in post-mitotic nuclear envelope assembly. EMBO J. 26:132-143.
18. Hynes, N. E., and H. A. Lane. 2005. ERBB receptors and cancer: the complexity of targeted inhibitors. Nat. Rev. Cancer. 5:341-354.
19. Ikediobi, O. N., H. Davies, G. Bignell, S. Edkins, C. Stevens, S. O'Meara, T. Santarius, T. Avis, S. Barthorpe, L. Brackenbury, G. Buck, A. Butler, J. Clements, J. Cole, E. Dicks, S. Forbes, K. Gray, K. Halliday, R. Harrison, K. Hills, J. Hinton, C. Hunter, A. Jenkinson, D. Jones, V. Kosmidou, R. Lugg, A. Menzies, T. Mironenko, A. Parker, J. Perry, K. Raine, D. Richardson, R. Shepherd, A. Small, R. Smith, H. Solomon, P. Stephens, J. Teague, C. Tofts, J. Varian, T. Webb, S. West, S. Widaa, A. Yates, W. Reinhold, J. N. Weinstein, M. R. Stratton, P. A. Futreal, and R. Wooster. 2006. Mutation analysis of 24 known cancer genes in the NCI-60 cell line set. Mol. Cancer Ther. 5:2606-2612.
20. Jagemann, L. R., L. G. Perez-Rivas, E. J. Ruiz, J. A. Ranea, F. Sanchez-Jimenez, A. R. Nebreda, E. Alba, and J. Lozano. 2008. The functional interaction of 14-3-3 proteins with the ERK1/2 scaffold KSR1 occurs in an isoform-specific manner. J. Biol. Chem. 283:17450-17462.
21. Kang, T. H., D. Y. Park, W. Kim, and K. T. Kim. 2008. VRK1 phosphorylates CREB and mediates CCND1 expression. J. Cell Sci. 121:3035-3041.
22. Karapetis, C. S., S. Khambata-Ford, D. J. Jonker, C. J. O'Callaghan, D. Tu, N. C. Tebbutt, R. J. Simes, H. Chalchal, J. D. Shapiro, S. Robitaille, T. J. Price, L. Shepherd, H. J. Au, C. Langer, M. J. Moore, and J. R. Zalcberg. 2008. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N. Engl. J. Med. 359:1757-1765.
23. Karreth, F. A., G. M. DeNicola, S. P. Winter, and D. A. Tuveson. 2009. C-Raf inhibits MAPK activation and transformation by B-Raf(V600E). Mol. Cell 36:477-486.
24. Kizaka-Kondoh, S., K. Sato, K. Tamura, H. Nojima, and H. Okayama. 1992. Raf-1 protein kinase is an integral component of the oncogenic signal cascade shared by epidermal growth factor and platelet-derived growth factor. Mol. Cell. Biol. 12:5078-5086.
25. Kjellman, M., L. Roshani, B. T. Teh, O. P. Kallioniemi, A. Hoog, S. Gray, L. O. Farnebo, M. Holst, M. Backdahl, and C. Larsson. 1999. Genotyping of adrenocortical tumors: very frequent deletions of the MEN1 locus in 11q13 and of a 1-centimorgan region in 2p16. J. Clin. Endocrinol. Metab. 84:730-735.
26. Klerkx, E. P., P. A. Lazo, and P. Askjaer. 2009. Emerging biological functions of the Vaccinia-Related Kinase (VRK) family. Histol. Histopathol. 24:749-759.
27. Klijn, J. G., M. P. Look, H. Portengen, J. Alexieva-Figusch, W. L. van Putten, and J. A. Foekens. 1994. The prognostic value of epidermal growth factor receptor (EGF-R) in primary breast cancer: results of a 10 year follow-up study. Breast Cancer Res. Treat. 29:73-83.
28. Kolch, W. 2005. Coordinating ERK/MAPK signalling through scaffolds and inhibitors. Nat. Rev. Mol. Cell Biol. 6:827-837.
29. Lopez-Borges, S., and P. A. Lazo. 2000. The human vaccinia-related kinase 1 (VRK1) phosphorylates threonine-18 within the mdm-2 binding site of the p53 tumour suppressor protein. Oncogene 19:3656-3664.
30. Martin, K. J., D. R. Patrick, M. J. Bissell, and M. V. Fournier. 2008. Prognostic breast cancer signature identified from 3D culture model accurately predicts clinical outcome across independent datasets. PLoS One 3:e2994.
31. Martinez-Carpio, P. A., C. Mur, P. Rosel, and M. A. Navarro. 1999. Constitutive and regulated secretion of epidermal growth factor and transforming growth factor-beta1 in MDA-MB-231 breast cancer cell line in 11-day cultures. Cell Signal. 11:753-757.
32. Martinez-Iglesias, O., S. Garcia-Silva, S. P. Tenbaum, J. Regadera, F. Larcher, J. M. Paramio, B. Vennstrom, and A. Aranda. 2009. Thyroid hormone receptor beta1 acts as a potent suppressor of tumor invasiveness and metastasis. Cancer Res. 69:501-509.
33. McKay, M. M., and D. K. Morrison. 2007. Integrating signals from RTKs to ERK/MAPK. Oncogene 26:3113-3121.
34. Michaloglou, C., L. C. Vredeveld, M. S. Soengas, C. Denoyelle, T. Kuilman, C. M. van der Horst, D. M. Majoor, J. W. Shay, W. J. Mooi, and D. S. Peeper. 2005. BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature 436:720-724.
35. Muller, J., S. Ory, T. Copeland, H. Piwnica-Worms, and D. K. Morrison. 2001. C-TAK1 regulates Ras signaling by phosphorylating the MAPK scaffold, KSR1. Mol. Cell 8:983-993. (Pubitemid 34031801)
36. Nichols, R. J., and P. Traktman. 2004. Characterization of three paralogous members of the mammalian vaccinia related kinase family. J. Biol. Chem. 279:7934-7946.
37. Nichols, R. J., M. S. Wiebe, and P. Traktman. 2006. The vaccinia-related kinases phosphorylate the N′ terminus of BAF, regulating its interaction with DNA and its retention in the nucleus. Mol. Biol. Cell 17:2451-2464.
38. Patton, E. E., H. R. Widlund, J. L. Kutok, K. R. Kopani, J. F. Amatruda, R. D. Murphey, S. Berghmans, E. A. Mayhall, D. Traver, C. D. Fletcher, J. C. Aster, S. R. Granter, A. T. Look, C. Lee, D. E. Fisher, and L. I. Zon. 2005. BRAF mutations are sufficient to promote nevi formation and cooperate with p53 in the genesis of melanoma. Curr. Biol. 15:249-254.
39. Rajakulendran, T., M. Sahmi, M. Lefrancois, F. Sicheri, and M. Therrien. 2009. A dimerization-dependent mechanism drives RAF catalytic activation. Nature 461:542-545.
40. Roberts, P. J., and C. J. Der. 2007. Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene 26:3291-3310.
41. Salerno, M., D. Palmieri, A. Bouadis, D. Halverson, and P. S. Steeg. 2005. Nm23-H1 metastasis suppressor expression level influences the binding properties, stability, and function of the kinase suppressor of Ras1 (KSR1) Erk scaffold in breast carcinoma cells. Mol. Cell. Biol. 25:1379-1388.
42. Santos, C. R., M. Rodriguez-Pinilla, F. M. Vega, J. L. Rodriguez-Peralto, S. Blanco, A. Sevilla, A. Valbuena, T. Hernandez, A. J. van Wijnen, F. Li, E. de Alava, M. Sanchez-Cespedes, and P. A. Lazo. 2006. VRK1 signaling pathway in the context of the proliferation phenotype in head and neck squamous cell carcinoma. Mol. Cancer Res. 4:177-185.
43. Sevilla, A., C. R. Santos, R. Barcia, F. M. Vega, and P. A. Lazo. 2004. c-Jun phosphorylation by the human vaccinia-related kinase 1 (VRK1) and its cooperation with the N-terminal kinase of c-Jun (JNK). Oncogene 23:8950-8958.
44. Sevilla, A., C. R. Santos, F. M. Vega, and P. A. Lazo. 2004. Human vaccinia-related kinase 1 (VRK1) activates the ATF2 transcriptional activity by novel phosphorylation on Thr-73 and Ser-62 and cooperates with JNK. J. Biol. Chem. 279:27458-27465.
45. Shin, S. Y., O. Rath, S. M. Choo, F. Fee, B. McFerran, W. Kolch, and K. H. Cho. 2009. Positive- and negative-feedback regulations coordinate the dynamic behavior of the Ras-Raf-MEK-ERK signal transduction pathway. J. Cell Sci. 122:425-435.
46. Valbuena, A., I. Lopez-Sanchez, and P. A. Lazo. 2008. Human VRK1 is an early response gene and its loss causes a block in cell cycle progression. PLoS One 3:e1642.
47. Valbuena, A., A. Suarez-Gauthier, F. Lopez-Rios, A. Lopez-Encuentra, S. Blanco, P. L. Fernandez, M. Sanchez-Cespedes, and P. A. Lazo. 2007. Alteration of the VRK1-p53 autoregulatory loop in human lung carcinomas. Lung Cancer 58:303-309.
48. Valbuena, A., F. M. Vega, S. Blanco, and P. A. Lazo. 2006. p53 downregulates its activating vaccinia-related kinase 1, forming a new autoregulatory loop. Mol. Cell. Biol. 26:4782-4793.
49. Vega, F. M., P. Gonzalo, M. L. Gaspar, and P. A. Lazo. 2003. Expression of the VRK (vaccinia-related kinase) gene family of p53 regulators in murine hematopoietic development. FEBS Lett. 544:176-180.
50. Vega, F. M., A. Sevilla, and P. A. Lazo. 2004. p53 stabilization and accumulation induced by human vaccinia-related kinase 1. Mol. Cell. Biol. 24:10366-10380.
51. Xing, H., K. Kornfeld, and A. J. Muslin. 1997. The protein kinase KSR interacts with 14-3-3 protein and Raf. Curr. Biol. 7:294-300.
52. Yarden, Y., and M. X. Sliwkowski. 2001. Untangling the ErbB signalling network. Nat. Rev. Mol. Cell Biol. 2:127-137.
53. Yuste, L., J. C. Montero, A. Esparis-Ogando, and A. Pandiella. 2005. Activation of ErbB2 by overexpression or by transmembrane neuregulin results in differential signaling and sensitivity to herceptin. Cancer Res. 65:6801-6810. (Pubitemid 41060718)
54. Zandi, R., A. B. Larsen, P. Andersen, M. T. Stockhausen, and H. S. Poulsen. 2007. Mechanisms for oncogenic activation of the epidermal growth factor receptor. Cell. Signal. 19:2013-2023.