Inhibiting the Recruitment of PLCγ1 to Kaposi’s Sarcoma Herpesvirus K15 Protein Reduces the Invasiveness and Angiogenesis of Infected Endothelial Cells

PLoS Pathogens

Volumn 11, Issue 8, 2015, Pages

  Gramolelli, Silvia ^a,b   Weidner Glunde, Magdalena ^a,b   Abere, Bizunesh ^a,b   Viejo Borbolla, Abel ^a   Bala, Kiran ^a   Rückert, Jessica ^a,b   Kremmer, Elisabeth ^c   Schulz, Thomas F ^a,b  

^a HANNOVER MEDICAL SCHOOL   (Germany)

^b HELMHOLTZ CENTRE FOR INFECTION RESEARCH   (Germany)

^c INSTITUTE OF EPIDEMIOLOGY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

FLUORESCEIN ISOTHIOCYANATE; HERPESVIRUS K15 PROTEIN; PHOSPHOLIPASE C GAMMA1; PHOSPHOLIPASE C GAMMA2; PROTEIN CDC42; RETROVIRUS VECTOR; UNCLASSIFIED DRUG; VIRUS PROTEIN; K15 PROTEIN, HUMAN HERPESVIRUS 8; PHOSPHOLIPASE C GAMMA; PLCG1 PROTEIN, HUMAN; VIRAL PROTEIN;

ANGIOGENESIS; ARTICLE; BINDING AFFINITY; CARBOXY TERMINAL SH2 BINDING MOTIF; CELL INVASION; CELL MIGRATION; CONTROLLED STUDY; GENE MUTATION; HEK293 CELL LINE; HUMAN; HUMAN CELL; HUMAN HERPESVIRUS 8; HUMAN TISSUE; IMMUNOFLUORESCENCE TEST; IMMUNOPRECIPITATION; KAPOSI SARCOMA; LUCIFERASE ASSAY; MICROARRAY ANALYSIS; MUTAGENESIS; NONHUMAN; PLASMID; PROTEIN BINDING; PROTEIN EXPRESSION; PROTEIN INTERACTION; PROTEIN PHOSPHORYLATION; PROTEIN STRUCTURE; SEQUENCE ANALYSIS; SIGNAL TRANSDUCTION; SURFACE PLASMON RESONANCE; WESTERN BLOTTING; ENDOTHELIUM CELL; FLUORESCENT ANTIBODY TECHNIQUE; GENETIC TRANSFECTION; METABOLISM; NEOVASCULARIZATION (PATHOLOGY); PATHOLOGY; TUMOR INVASION;

BLOTTING, WESTERN; ENDOTHELIAL CELLS; FLUORESCENT ANTIBODY TECHNIQUE; HERPESVIRUS 8, HUMAN; HUMANS; IMMUNOPRECIPITATION; NEOPLASM INVASIVENESS; NEOVASCULARIZATION, PATHOLOGIC; PHOSPHOLIPASE C GAMMA; SARCOMA, KAPOSI; SURFACE PLASMON RESONANCE; TRANSFECTION; VIRAL PROTEINS;

EID: 84940783354     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1005105     Document Type: Article

References (61)

1. Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, et al. (1994) Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science 266: 1865–1869. 7997879
2. Chang Y, Moore P, (2014) Twenty years of KSHV. Viruses 6: 4258–4264. doi: 10.3390/v6114258 25386844
3. Cesarman E, Chang Y, Moore PS, Said JW, Knowles DM, (1995) Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. N Engl J Med 332: 1186–1191. 7700311
4. Soulier J, Grollet L, Oksenhendler E, Cacoub P, Cazals-Hatem D, et al. (1995) Kaposi's sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman's disease. Blood 86: 1276–1280. 7632932
5. Parkin DM, Bray F, Ferlay J, Jemal A, (2014) Cancer in Africa 2012. Cancer Epidemiol Biomarkers Prev 23: 953–966. doi: 10.1158/1055-9965.EPI-14-0281 24700176
6. Rios A, (2014) HIV-Related Hematological Malignancies: A Concise Review. Clin Lymphoma Myeloma Leuk 14S: S96–S103.
7. Orenstein JM, (2008) Ultrastructure of Kaposi sarcoma. Ultrastruct Pathol 32: 211–220. doi: 10.1080/01913120802343871 18958795
8. Ensoli B, Sturzl M, (1998) Kaposi's sarcoma: a result of the interplay among inflammatory cytokines, angiogenic factors and viral agents. Cytokine Growth Factor Rev 9: 63–83. 9720757
9. Ojala PM, Schulz TF, (2014) Manipulation of endothelial cells by KSHV: implications for angiogenesis and aberrant vascular differentiation. Semin Cancer Biol 26: 69–77. doi: 10.1016/j.semcancer.2014.01.008 24486643
10. Staskus KA, Zhong W, Gebhard K, Herndier B, Wang H, et al. (1997) Kaposi's sarcoma-associated herpesvirus gene expression in endothelial (spindle) tumor cells. J Virol 71: 715–719. 8985403
11. Ensoli B, Sturzl M, Monini P, (2000) Cytokine-mediated growth promotion of Kaposi's sarcoma and primary effusion lymphoma. Semin Cancer Biol 10: 367–381. 11100885
12. Haas DA, Bala K, Busche G, Weidner-Glunde M, Santag S, et al. (2013) The inflammatory kinase MAP4K4 promotes reactivation of Kaposi's sarcoma herpesvirus and enhances the invasiveness of infected endothelial cells. PLoS Pathog 9: e1003737. doi: 10.1371/journal.ppat.1003737 24244164
13. Rosano L, Spinella F, Di Castro V, Nicotra MR, Albini A, et al. (2003) Endothelin receptor blockade inhibits molecular effectors of Kaposi's sarcoma cell invasion and tumor growth in vivo. Am J Pathol 163: 753–762. 12875994
14. Douglas JL, Gustin JK, Dezube B, Pantanowitz JL, Moses AV, (2007) Kaposi's sarcoma: a model of both malignancy and chronic inflammation. Panminerva Med 49: 119–138. 17912148
15. Qian LW, Xie J, Ye F, Gao SJ, (2007) Kaposi's sarcoma-associated herpesvirus infection promotes invasion of primary human umbilical vein endothelial cells by inducing matrix metalloproteinases. J Virol 81: 7001–7010. 17442715
16. Douglas JL, Gustin JK, Moses AV, Dezube BJ, Pantanowitz L, (2010) Kaposi Sarcoma Pathogenesis: A Triad of Viral Infection, Oncogenesis and Chronic Inflammation. Transl Biomed 1. 23082307
17. Bala K, Bosco R, Gramolelli S, Haas DA, Kati S, et al. (2012) Kaposi's sarcoma herpesvirus K15 protein contributes to virus-induced angiogenesis by recruiting PLCgamma1 and activating NFAT1-dependent RCAN1 expression. PLoS Pathog 8: e1002927. doi: 10.1371/journal.ppat.1002927 23028325
18. Choi JK, Lee BS, Shim SN, Li M, Jung JU, (2000) Identification of the novel K15 gene at the rightmost end of the Kaposi's sarcoma-associated herpesvirus genome. J Virol 74: 436–446. 10590133
19. Glenn M, Rainbow L, Aurade F, Davison A, Schulz TF, (1999) Identification of a spliced gene from Kaposi's sarcoma-associated herpesvirus encoding a protein with similarities to latent membrane proteins 1 and 2A of Epstein-Barr virus. J Virol 73: 6953–6963. 10400794
20. Poole LJ, Zong JC, Ciufo DM, Alcendor DJ, Cannon JS, et al. (1999) Comparison of genetic variability at multiple loci across the genomes of the major subtypes of Kaposi's sarcoma-associated herpesvirus reveals evidence for recombination and for two distinct types of open reading frame K15 alleles at the right-hand end. J Virol 73: 6646–6660. 10400762
21. Kakoola DN, Sheldon J, Byabazaire N, Bowden RJ, Katongole-Mbidde E, et al. (2001) Recombination in human herpesvirus-8 strains from Uganda and evolution of the K15 gene. J Gen Virol 82: 2393–2404. 11562533
22. Brinkmann MM, Glenn M, Rainbow L, Kieser A, Henke-Gendo C, et al. (2003) Activation of mitogen-activated protein kinase and NF-kappaB pathways by a Kaposi's sarcoma-associated herpesvirus K15 membrane protein. J Virol 77: 9346–9358. 12915550
23. Havemeier A, Gramolelli S, Pietrek M, Jochmann R, Sturzl M, et al. (2014) Activation of NF-kappaB by the Kaposi's sarcoma-associated herpesvirus K15 protein involves recruitment of the NF-kappaB-inducing kinase, IkappaB kinases, and phosphorylation of p65. J Virol 88: 13161–13172. doi: 10.1128/JVI.01766-14 25187543
24. Wang L, Pietrek M, Brinkmann MM, Havemeier A, Fischer I, et al. (2009) Identification and functional characterization of a spliced rhesus rhadinovirus gene with homology to the K15 gene of Kaposi's sarcoma-associated herpesvirus. J Gen Virol 90: 1190–1201. doi: 10.1099/vir.0.007971-0 19264656
25. Brinkmann MM, Pietrek M, Dittrich-Breiholz O, Kracht M, Schulz TF, (2007) Modulation of host gene expression by the K15 protein of Kaposi's sarcoma-associated herpesvirus. J Virol 81: 42–58. 17050609
26. Sala G, Dituri F, Raimondi C, Previdi S, Maffucci T, et al. (2008) Phospholipase Cgamma1 is required for metastasis development and progression. Cancer Res 68: 10187–10196. doi: 10.1158/0008-5472.CAN-08-1181 19074886
27. Jones NP, Katan M, (2007) Role of phospholipase Cgamma1 in cell spreading requires association with a beta-Pix/GIT1-containing complex, leading to activation of Cdc42 and Rac1. Mol Cell Biol 27: 5790–5805. 17562871
28. Jones NP, Peak J, Brader S, Eccles SA, Katan M, (2005) PLCgamma1 is essential for early events in integrin signalling required for cell motility. J Cell Sci 118: 2695–2706. 15944397
29. Kassis J, Lauffenburger DA, Turner T, Wells A, (2001) Tumor invasion as dysregulated cell motility. Semin Cancer Biol 11: 105–117. 11322830
30. Kassis J, Moellinger J, Lo H, Greenberg NM, Kim HG, et al. (1999) A role for phospholipase C-gamma-mediated signaling in tumor cell invasion. Clin Cancer Res 5: 2251–2260. 10473113
31. Lattanzio R, Marchisio M, La Sorda R, Tinari N, Falasca M, et al. (2013) Overexpression of activated phospholipase Cgamma1 is a risk factor for distant metastases in T1–T2, N0 breast cancer patients undergoing adjuvant chemotherapy. Int J Cancer 132: 1022–1031. doi: 10.1002/ijc.27751 22847294
32. Lattanzio R, Piantelli M, Falasca M, (2013) Role of phospholipase C in cell invasion and metastasis. Adv Biol Regul 53: 309–318. doi: 10.1016/j.jbior.2013.07.006 23925006
33. Kunze K, Spieker T, Gamerdinger U, Nau K, Berger J, et al. (2014) A recurrent activating PLCG1 mutation in cardiac angiosarcomas increases apoptosis resistance and invasiveness of endothelial cells. Cancer Res 74: 6173–6183. doi: 10.1158/0008-5472.CAN-14-1162 25252913
34. Behjati S, Tarpey PS, Sheldon H, Martincorena I, Van Loo P, et al. (2014) Recurrent PTPRB and PLCG1 mutations in angiosarcoma. Nat Genet 46: 376–379. doi: 10.1038/ng.2921 24633157
35. Koss H, Bunney TD, Behjati S, Katan M, (2014) Dysfunction of phospholipase Cgamma in immune disorders and cancer. Trends Biochem Sci 39: 603–611. doi: 10.1016/j.tibs.2014.09.004 25456276
36. Sharp TV, Wang HW, Koumi A, Hollyman D, Endo Y, et al. (2002) K15 protein of Kaposi's sarcoma-associated herpesvirus is latently expressed and binds to HAX-1, a protein with antiapoptotic function. J Virol 76: 802–816. 11752170
37. Tsai YH, Wu MF, Wu YH, Chang SJ, Lin SF, et al. (2009) The M type K15 protein of Kaposi's sarcoma-associated herpesvirus regulates microRNA expression via its SH2-binding motif to induce cell migration and invasion. J Virol 83: 622–632. doi: 10.1128/JVI.00869-08 18971265
38. Manabe R, Kovalenko M, Webb DJ, Horwitz AR, (2002) GIT1 functions in a motile, multi-molecular signaling complex that regulates protrusive activity and cell migration. J Cell Sci 115: 1497–1510. 11896197
39. Chattopadhyay A, Vecchi M, Ji Q, Mernaugh R, Carpenter G, (1999) The role of individual SH2 domains in mediating association of phospholipase C-gamma1 with the activated EGF receptor. J Biol Chem 274: 26091–26097. 10473558
40. Katan M, Williams RL, (1997) Phosphoinositide-specific phospholipase C: structural basis for catalysis and regulatory interactions. Semin Cell Dev Biol 8: 287–296. 10024492
41. Scott JD, Pawson T, (2009) Cell signaling in space and time: where proteins come together and when they're apart. Science 326: 1220–1224. doi: 10.1126/science.1175668 19965465
42. Liu BA, Engelmann BW, Nash PD, (2012) The language of SH2 domain interactions defines phosphotyrosine-mediated signal transduction. FEBS Lett 586: 2597–2605. doi: 10.1016/j.febslet.2012.04.054 22569091
43. Liu BA, Jablonowski K, Shah EE, Engelmann BW, Jones RB, et al. (2010) SH2 domains recognize contextual peptide sequence information to determine selectivity. Mol Cell Proteomics 9: 2391–2404. doi: 10.1074/mcp.M110.001586 20627867
44. Ji QS, Winnier GE, Niswender KD, Horstman D, Wisdom R, et al. (1997) Essential role of the tyrosine kinase substrate phospholipase C-gamma1 in mammalian growth and development. Proc Natl Acad Sci U S A 94: 2999–3003. 9096335
45. Decker C, Hesker P, Zhang K, Faccio R, (2013) Targeted inhibition of phospholipase C gamma2 adaptor function blocks osteoclastogenesis and protects from pathological osteolysis. J Biol Chem 288: 33634–33641. doi: 10.1074/jbc.M113.477281 24081142
46. Kaneko T, Huang H, Cao X, Li X, Li C, et al. (2012) Superbinder SH2 domains act as antagonists of cell signaling. Sci Signal 5: ra68. 23012655
47. DeBell K, Graham L, Reischl I, Serrano C, Bonvini E, et al. (2007) Intramolecular regulation of phospholipase C-gamma1 by its C-terminal Src homology 2 domain. Mol Cell Biol 27: 854–863. 17116690
48. Gresset A, Hicks SN, Harden TK, Sondek J, (2010) Mechanism of phosphorylation-induced activation of phospholipase C-gamma isozymes. J Biol Chem 285: 35836–35847. doi: 10.1074/jbc.M110.166512 20807769
49. Gramolelli S, Schulz TF, (2015) The role of Kaposi sarcoma-associated herpesvirus in the pathogenesis of Kaposi sarcoma. J Pathol 235: 368–380. doi: 10.1002/path.4441 25212381
50. Frank SR, Hansen SH, (2008) The PIX-GIT complex: a G protein signaling cassette in control of cell shape. Semin Cell Dev Biol 19: 234–244. doi: 10.1016/j.semcdb.2008.01.002 18299239
51. Hoefen RJ, Berk BC, (2006) The multifunctional GIT family of proteins. J Cell Sci 119: 1469–1475. 16598076
52. Vieira J, O'Hearn PM, (2004) Use of the red fluorescent protein as a marker of Kaposi's sarcoma-associated herpesvirus lytic gene expression. Virology 325: 225–240. 15246263
53. Bunney TD, Esposito D, Mas-Droux C, Lamber E, Baxendale RW, et al. (2012) Structural and functional integration of the PLCgamma interaction domains critical for regulatory mechanisms and signaling deregulation. Structure 20: 2062–2075. doi: 10.1016/j.str.2012.09.005 23063561
54. Chen P, Xie H, Sekar MC, Gupta K, Wells A, (1994) Epidermal growth factor receptor-mediated cell motility: phospholipase C activity is required, but mitogen-activated protein kinase activity is not sufficient for induced cell movement. J Cell Biol 127: 847–857. 7962064
55. Wang L, Damania B, (2008) Kaposi's sarcoma-associated herpesvirus confers a survival advantage to endothelial cells. Cancer Res 68: 4640–4648. doi: 10.1158/0008-5472.CAN-07-5988 18559509
56. Wang L, Brinkmann MM, Pietrek M, Ottinger M, Dittrich-Breiholz O, et al. (2007) Functional characterization of the M-type K15-encoded membrane protein of Kaposi's sarcoma-associated herpesvirus. J Gen Virol 88: 1698–1707. 17485529
57. Jaffe EA, Nachman RL, Becker CG, Minick CR, (1973) Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest 52: 2745–2756. 4355998
58. May T, Butueva M, Bantner S, Markusic D, Seppen J, et al. (2010) Synthetic gene regulation circuits for control of cell expansion. Tissue Eng Part A 16: 441–452. doi: 10.1089/ten.TEA.2009.0184 19705962
59. Alkharsah KR, Singh VV, Bosco R, Santag S, Grundhoff A, et al. (2011) Deletion of Kaposi's sarcoma-associated herpesvirus FLICE inhibitory protein, vFLIP, from the viral genome compromises the activation of STAT1-responsive cellular genes and spindle cell formation in endothelial cells. J Virol 85: 10375–10388. doi: 10.1128/JVI.00226-11 21795355
60. Kati S, Hage E, Mynarek M, Ganzenmueller T, Indenbirken D, et al. (2015) Generation of high-titre virus stocks using BrK.219, a B-cell line infected stably with recombinant Kaposi's sarcoma-associated herpesvirus. J Virol Methods.
61. Carpenter AE, Jones TR, Lamprecht MR, Clarke C, Kang IH, et al. (2006) CellProfiler: image analysis software for identifying and quantifying cell phenotypes. Genome Biol 7: R100. 17076895