Signaling through the P38 and ERK pathways: A common link between HIV replication and the immune response

Immunologic Research

Volumn 48, Issue 1-3, 2010, Pages 99-109

  Furler, Robert L ^a   Uittenbogaart, Christel H ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Activation; Cytokines; ERK; HIV; IL 10; IL 2; Immunosuppression; P38; Proinflammatory; TNF

Indexed keywords

CHEMOKINE RECEPTOR; FAS ANTIGEN; FAS LIGAND; GELATINASE B; GLYCOPROTEIN GP 120; INTERLEUKIN 10; INTERLEUKIN 2; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; NEF PROTEIN; PROGRAMMED DEATH 1 RECEPTOR; SYNAPTOPHYSIN; T LYMPHOCYTE RECEPTOR; TRANSACTIVATOR PROTEIN; TRANSCRIPTION FACTOR; TRANSFORMING GROWTH FACTOR BETA1; TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND; VIRUS PROTEIN;

APOPTOSIS; CD4+ T LYMPHOCYTE; CELL ACTIVATION; CELL CYCLE ARREST; CELL CYCLE PROGRESSION; CELL PROLIFERATION; CELL SURVIVAL; CYTOKINE PRODUCTION; DISEASE COURSE; ENZYME INDUCTION; ENZYME REGULATION; HOST CELL; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNE RESPONSE; IMMUNE SYSTEM; IMMUNOPATHOGENESIS; IMMUNOREGULATION; INTRACELLULAR SIGNALING; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN MOTIF; PROTEIN PHOSPHORYLATION; RECEPTOR DOWN REGULATION; REVIEW; SIGNAL TRANSDUCTION; T LYMPHOCYTE ACTIVATION; VIRION; VIRUS CELL INTERACTION; VIRUS REPLICATION; VIRUS TRANSCRIPTION;

ANTIGENS, CD4; APOPTOSIS; CD4-POSITIVE T-LYMPHOCYTES; CYTOKINES; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; HIV ENVELOPE PROTEIN GP120; HIV INFECTIONS; HIV-1; HUMANS; LYMPHOCYTE ACTIVATION; P38 MITOGEN-ACTIVATED PROTEIN KINASES; RECEPTORS, CYTOKINE; RECEPTORS, HIV; SIGNAL TRANSDUCTION; VIRUS REPLICATION;

EID: 78549281377     PISSN: 0257277X     EISSN: None     Source Type: Journal    
DOI: 10.1007/s12026-010-8170-1     Document Type: Review

References (79)

1. SA Klein, et al. 1997 Demonstration of the Th1 to Th2 cytokine shift during the course of HIV-1 infection using cytoplasmic cytokine detection on single cell level by flow cytometry AIDS 11 1111 1118 1:STN:280: DyaK2sznslymtQ%3D%3D 10.1097/00002030-199709000-00005 9233457 (Pubitemid 27273607)
2. M Alfano G Poli 2005 Role of cytokines and chemokines in the regulation of innate immunity and HIV infection Mol Immunol 42 161 182 1:CAS:528: DC%2BD2cXosFSmsb8%3D 10.1016/j.molimm.2004.06.016 15488606 (Pubitemid 39361447)
3. K Muthumani, et al. 2008 Human immunodeficiency virus type 1 Nef induces programmed death 1 expression through a p38 mitogen-activated protein kinase-dependent mechanism J Virol 82 11536 11544 1:CAS:528:DC%2BD1cXhsVaqsr3E 10.1128/JVI.00485-08 18799583
4. T Vollbrecht, et al. 2010 Impact of changes in antigen level on CD38/PD-1 co-expression on HIV-specific CD8 T cells in chronic, untreated HIV-1 infection J Med Virol 82 358 370 1:CAS:528:DC%2BC3cXitlKntrY%3D 10.1002/jmv.21723 20087935
5. K Muthumani, et al. 2005 HIV-1 Nef-induced FasL induction and bystander killing requires p38 MAPK activation Blood 106 2059 2068 1:CAS:528: DC%2BD2MXhtVWksLrJ 10.1182/blood-2005-03-0932 15928037 (Pubitemid 41291720)
6. AR Stacey, et al. 2009 Induction of a striking systemic cytokine cascade prior to peak viremia in acute human immunodeficiency virus type 1 infection, in contrast to more modest and delayed responses in acute hepatitis B and C virus infections J Virol 83 3719 3733 1:CAS:528:DC%2BD1MXktlSju7k%3D 10.1128/JVI.01844-08 19176632
7. C Graziosi, et al. 1996 Kinetics of cytokine expression during primary human immunodeficiency virus type 1 infection Proc Natl Acad Sci USA 93 4386 4391 1:CAS:528:DyaK28XivVKqt7o%3D 10.1073/pnas.93.9.4386 8633076 (Pubitemid 26144297)
8. MA Ostrowski, et al. 2001 Quantitative and qualitative assessment of human immunodeficiency virus type 1 (HIV-1)-specific CD4+ T cell immunity to gag in HIV-1-infected individuals with differential disease progression: reciprocal interferon-gamma and interleukin-10 responses J Infect Dis 184 1268 1278 1:CAS:528:DC%2BD3MXpt1Whs7c%3D 10.1086/324005 11679915 (Pubitemid 33055571)
9. S Gupta R Boppana GC Mishra B Saha D Mitra 2008 HIV-1 Tat suppresses gp120-specific T cell response in IL-10-dependent manner J Immunol 180 79 88 1:CAS:528:DC%2BD2sXhsVGjurfN 18097007
10. MA Brockman, et al. 2009 IL-10 is up-regulated in multiple cell types during viremic HIV infection and reversibly inhibits virus-specific T cells Blood 114 346 356 1:CAS:528:DC%2BD1MXovVKlsrw%3D 10.1182/blood-2008-12-191296 19365081
11. JM Kyriakis J Avruch 2001 Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation Physiol Rev 81 807 869 1:CAS:528:DC%2BD3MXislCrsb8%3D 11274345
12. M Krishna H Narang 2008 The complexity of mitogen-activated protein kinases (MAPKs) made simple Cell Mol Life Sci 65 3525 3544 1:CAS:528: DC%2BD1cXhtlyit7vL 10.1007/s00018-008-8170-7 18668205
13. PP Roux J Blenis 2004 ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions Microbiol Mol Biol Rev 68 320 344 1:CAS:528:DC%2BD2cXlsl2hu7Y%3D 10.1128/MMBR.68.2.320-344.2004 15187187 (Pubitemid 38756868)
14. T Shimo, et al. 2007 Specific inhibitor of MEK-mediated cross-talk between ERK and p38 MAPK during differentiation of human osteosarcoma cells J Cell Commun Signal 1 103 111 10.1007/s12079-007-0010-2 18481201
15. Z Wang, et al. 2006 Phosphatase-mediated crosstalk control of ERK and p38 MAPK signaling in corneal epithelial cells Invest Ophthalmol Vis Sci 47 5267 5275 10.1167/iovs.06-0642 17122112 (Pubitemid 46723774)
16. F Dodeller H Schulze-Koops 2006 The p38 mitogen-activated protein kinase signaling cascade in CD4 T cells Arthritis Res Ther 8 205 10.1186/ar1905 16542479
17. JC Lee PR Young 1996 Role of CSB/p38/RK stress response kinase in LPS and cytokine signaling mechanisms J Leukoc Biol 59 152 157 1:CAS:528: DyaK28XhtlKgurk%3D 8603987
18. JD Ashwell 2006 The many paths to p38 mitogen-activated protein kinase activation in the immune system Nat Rev Immunol 6 532 540 1:CAS:528: DC%2BD28XmtFegsLY%3D 10.1038/nri1865 16799472 (Pubitemid 43980525)
19. RN Saha M Jana K Pahan 2007 MAPK p38 regulates transcriptional activity of NF-kappaB in primary human astrocytes via acetylation of p65 J Immunol 179 7101 7109 1:CAS:528:DC%2BD2sXht1Crs7jF 17982102
20. JL Perfettini, et al. 2005 Essential role of p53 phosphorylation by p38 MAPK in apoptosis induction by the HIV-1 envelope J Exp Med 201 279 289 1:CAS:528:DC%2BD2MXot12lsw%3D%3D 10.1084/jem.20041502 15642743 (Pubitemid 40189437)
21. PS Cohen, et al. 1997 The critical role of p38 MAP kinase in T cell HIV-1 replication Mol Med 3 339 346 1:CAS:528:DyaK2sXktVymtLs%3D 9205949
22. K Muthumani, et al. 2004 Suppression of HIV-1 viral replication and cellular pathogenesis by a novel p38/JNK kinase inhibitor AIDS 18 739 748 1:CAS:528:DC%2BD2cXksVWhu7o%3D 10.1097/00002030-200403260-00004 15075508 (Pubitemid 38535001)
23. M Kadoki BI Choi Y Iwakura, et al. 2010 The mechanism of LPS-induced HIV type I activation in transgenic mouse macrophages Int Immunol 22 469 478 1:CAS:528:DC%2BC3cXms1Oms7Y%3D 10.1093/intimm/dxq032 20504885
24. D Gutierrez-Sanmartin, et al. 2008 Implication of p38 mitogen-activated protein kinase isoforms (alpha, beta, gamma and delta) in CD4+ T-cell infection with human immunodeficiency virus type I J Gen Virol 89 1661 1671 1:CAS:528:DC%2BD1cXot1yjs74%3D 10.1099/vir.0.82971-0 18559936
25. R Horie, et al. 2007 TRAF activation of C/EBPbeta (NF-IL6) via p38 MAPK induces HIV-1 gene expression in monocytes/macrophages Microbes Infect 9 721 728 1:CAS:528:DC%2BD2sXkvFGqsLk%3D 10.1016/j.micinf.2007.02.017 17409010 (Pubitemid 46660684)
26. L Shapiro KA Heidenreich MK Meintzer CA Dinarello 1998 Role of p38 mitogen-activated protein kinase in HIV type 1 production in vitro Proc Natl Acad Sci USA 95 7422 7426 1:CAS:528:DyaK1cXktFChtLg%3D 10.1073/pnas.95.13.7422 9636165 (Pubitemid 28293268)
27. S Kumar, et al. 1996 Activation of the HIV-1 long terminal repeat by cytokines and environmental stress requires an active CSBP/p38 MAP kinase J Biol Chem 271 30864 30869 1:CAS:528:DyaK28Xntlarsro%3D 10.1074/jbc.271.48.30864 8940070 (Pubitemid 26404110)
28. SA Trushin, et al. 2007 Glycoprotein 120 binding to CXCR4 causes p38-dependent primary T cell death that is facilitated by, but does not require cell-associated CD4 J Immunol 178 4846 4853 1:CAS:528:DC%2BD2sXjslWjs7Y%3D 17404265
29. M Kaul SA Lipton 1999 Chemokines and activated macrophages in HIV gp120-induced neuronal apoptosis Proc Natl Acad Sci USA 96 8212 8216 1:CAS:528:DyaK1MXltVOrsb8%3D 10.1073/pnas.96.14.8212 10393974 (Pubitemid 29328434)
30. CE Rudd 2005 MAPK p38: alternative and nonstressful in T cells Nat Immunol 6 368 370 1:CAS:528:DC%2BD2MXisVyitL8%3D 10.1038/ni0405-368 15785766 (Pubitemid 41716776)
31. E Jacotot, et al. 1997 HIV-1 envelope glycoproteins-mediated apoptosis is regulated by CD4 dependent and independent mechanisms Apoptosis 2 47 60 1:CAS:528:DyaK2sXjtVOhtLo%3D 10.1023/A:1026435625144 14646564
32. AA Kapasi G Patel N Franki PC Singhal 2002 HIV-1 gp120-induced tubular epithelial cell apoptosis is mediated through p38-MAPK phosphorylation Mol Med 8 676 685 1:CAS:528:DC%2BD3sXps1WmsA%3D%3D 12520084
33. NA Khan F Di Cello M Stins KS Kim 2007 Gp120-mediated cytotoxicity of human brain microvascular endothelial cells is dependent on p38 mitogen-activated protein kinase activation J Neurovirol 13 242 251 1:CAS:528:DC%2BD2sXnt1Wjs78%3D 10.1080/13550280701286531 17613714 (Pubitemid 47050650)
34. IN Singh, et al. 2005 Differential involvement of p38 and JNK MAP kinases in HIV-1 Tat and gp120-induced apoptosis and neurite degeneration in striatal neurons Neuroscience 135 781 790 1:CAS:528:DC%2BD2MXhtVymtr3L 10.1016/j.neuroscience.2005.05.028 16111829 (Pubitemid 41407741)
35. M Kaul Q Ma KE Medders MK Desai SA Lipton 2007 IV-1 coreceptors CCR5 and CXCR4 both mediate neuronal cell death but CCR5 paradoxically can also contribute to protection Cell Death Differ 14 296 305 1:CAS:528: DC%2BD2sXkslChtg%3D%3D 10.1038/sj.cdd.4402006 16841089 (Pubitemid 46092232)
36. JL Perfettini, et al. 2008 Critical involvement of the ATM-dependent DNA damage response in the apoptotic demise of HIV-1-elicited syncytia PLoS One 3 e2458 10.1371/journal.pone.0002458 18560558
37. ML Gougeon M Piacentini 2009 New insights on the role of apoptosis and autophagy in HIV pathogenesis Apoptosis 14 501 508 1:CAS:528: DC%2BD1MXivFSnsL4%3D 10.1007/s10495-009-0314-1 19199038
38. H Cha X Wang H Li AJ Fornace Jr 2007 A functional role for p38 MAPK in modulating mitotic transit in the absence of stress J Biol Chem 282 22984 22992 1:CAS:528:DC%2BD2sXot1Wit74%3D 10.1074/jbc.M700735200 17548358 (Pubitemid 47267360)
39. A Mikhailov D Patel DJ McCance CL Rieder 2007 The G2 p38-mediated stress-activated checkpoint pathway becomes attenuated in transformed cells Curr Biol 17 2162 2168 1:CAS:528:DC%2BD2sXhsVCksb3K 10.1016/j.cub.2007.11.028 18060783 (Pubitemid 350236862)
40. S Okamoto, et al. 2007 HIV/gp120 decreases adult neural progenitor cell proliferation via checkpoint kinase-mediated cell-cycle withdrawal and G1 arrest Cell Stem Cell 1 230 236 1:CAS:528:DC%2BD2sXhtVSnsrjP 10.1016/j.stem.2007.07. 010 18371353 (Pubitemid 47215594)
41. D Misse, et al. 2001 HIV-1 glycoprotein 120 induces the MMP-9 cytopathogenic factor production that is abolished by inhibition of the p38 mitogen-activated protein kinase signaling pathway Blood 98 541 547 1:CAS:528:DC%2BD3MXlsFKrt7c%3D 10.1182/blood.V98.3.541 11468147
42. K Leghmari X Contreras C Moureau E Bahraoui 2008 HIV-1 Tat protein induces TNF-alpha and IL-10 production by human macrophages: differential implication of PKC-betaII and -delta isozymes and MAP kinases ERK1/2 and p38 Cell Immunol 254 46 55 1:CAS:528:DC%2BD1cXhtlGhtrfL 10.1016/j.cellimm.2008.06. 011 18692180
43. Kumawat K, Pathak SK, Spetz AL, Kundu M, Basu J. Exogenous Nef is an inhibitor of Mycobacterium tuberculosis-induced tumor necrosis factor-alpha production and macrophage apoptosis. J Biol Chem. 285:12629-12637.
44. K Leghmari Y Bennasser J Tkaczuk E Bahraoui 2008 HIV-1 Tat protein induces IL-10 production by an alternative TNF-alpha-independent pathway in monocytes: role of PKC-delta and p38 MAP kinase Cell Immunol 253 45 53 1:CAS:528:DC%2BD1cXhtFWlsrzP 10.1016/j.cellimm.2008.04.015 18541226
45. K Gee JB Angel S Mishra MA Blahoianu A Kumar 2007 IL-10 regulation by HIV-Tat in primary human monocytic cells: involvement of calmodulin/calmodulin- dependent protein kinase-activated p38 MAPK and Sp-1 and CREB-1 transcription factors J Immunol 178 798 807 1:CAS:528:DC%2BD2sXhvVajsA%3D%3D 17202341
46. JC Li AS Lau 2007 A role for mitogen-activated protein kinase and Ets-1 in the induction of interleukin-10 transcription by human immunodeficiency virus-1 Tat Immunology 121 337 348 1:CAS:528:DC%2BD2sXntV2ksro%3D 10.1111/j.1365-2567.2007.02580.x 17376198 (Pubitemid 46817355)
47. K Leghmari Y Bennasser E Bahraoui 2008 HIV-1 Tat protein induces IL-10 production in monocytes by classical and alternative NF-kappaB pathways Eur J Cell Biol 87 947 962 1:CAS:528:DC%2BD1MXhtlyksA%3D%3D 10.1016/j.ejcb.2008.06.005 18760861
48. O Kogkopoulou, et al. 2006 Conditional up-regulation of IL-2 production by p38 MAPK inactivation is mediated by increased Erk1/2 activity J Leukoc Biol 79 1052 1060 1:CAS:528:DC%2BD28XksVKqsrk%3D 10.1189/jlb.0705418 16478922 (Pubitemid 44835592)
49. A Wiercinska-Drapalo R Flisiak J Jaroszewicz D Prokopowicz 2004 Increased plasma transforming growth factor-beta1 is associated with disease progression in HIV-1-infected patients Viral Immunol 17 109 113 1:CAS:528: DC%2BD2cXhvFakt7c%3D 10.1089/088282404322875502 15018667 (Pubitemid 38338467)
50. S Kuerten, et al. 2008 The TRAIL of helpless CD8+ T cells in HIV infection AIDS Res Hum Retroviruses 24 1175 1183 1:CAS:528:DC%2BD1cXhtFWltbvL 10.1089/aid.2008.0062 18729775
51. PJ Roberts CJ Der 2007 Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer Oncogene 26 3291 3310 1:CAS:528:DC%2BD2sXlt1Wktb4%3D 10.1038/sj.onc.1210422 17496923 (Pubitemid 46763022)
52. AD Sharrocks 2006 Cell cycle: sustained ERK signalling represses the inhibitors Curr Biol 16 R540 R542 1:CAS:528:DC%2BD28XntlCrtbs%3D 10.1016/j.cub.2006.06.038 16860730 (Pubitemid 44066782)
53. TH Holmstrom, et al. 2000 MAPK/ERK signaling in activated T cells inhibits CD95/Fas-mediated apoptosis downstream of DISC assembly EMBO J 19 5418 5428 1:CAS:528:DC%2BD3cXotFKqtbs%3D 10.1093/emboj/19.20.5418 11032809
54. D Langford R Hurford M Hashimoto M Digicaylioglu E Masliah 2005 Signalling crosstalk in FGF2-mediated protection of endothelial cells from HIV-gp120 BMC Neurosci 6 8 10.1186/1471-2202-6-8 15689238 (Pubitemid 41418266)
55. CJ Marshall 1995 Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation Cell 80 179 185 1:CAS:528:DyaK2MXjtlGnsr8%3D 10.1016/0092-8674(95)90401-8 7834738
56. Dumaz N, Marais R. Integrating signals between cAMP and the RAS/RAF/MEK/ERK signalling pathways. Based on the anniversary prize of the Gesellschaft fur Biochemie und Molekularbiologie Lecture delivered on 5 July 2003 at the Special FEBS Meeting in Brussels. FEBS J. 2005; 272:3491-3504.
57. RD York, et al. 1998 Rap1 mediates sustained MAP kinase activation induced by nerve growth factor Nature 392 622 626 1:CAS:528:DyaK1cXis1Wjtrs%3D 10.1038/33451 9560161 (Pubitemid 28207722)
58. H Tsukamoto A Irie Y Nishimura 2004 B-Raf contributes to sustained extracellular signal-regulated kinase activation associated with interleukin-2 production stimulated through the T cell receptor J Biol Chem 279 48457 48465 1:CAS:528:DC%2BD2cXptl2msL4%3D 10.1074/jbc.M403087200 15339934 (Pubitemid 39541004)
59. Q Liu PA Hofmann 2004 Protein phosphatase 2A-mediated cross-talk between p38 MAPK and ERK in apoptosis of cardiac myocytes Am J Physiol Heart Circ Physiol 286 H2204 H2212 1:CAS:528:DC%2BD2cXkvFCrtL8%3D 10.1152/ajpheart.01050. 2003 14962831 (Pubitemid 38685234)
60. T Koike, et al. 2003 A novel ERK-dependent signaling process that regulates interleukin-2 expression in a late phase of T cell activation J Biol Chem 278 15685 15692 1:CAS:528:DC%2BD3sXjt1eiu7o%3D 10.1074/jbc.M210829200 12595531 (Pubitemid 36799679)
61. Makedonas G et al. Perforin and IL-2 upregulation define qualitative differences among highly functional virus-specific human CD8 T cells. PLoS Pathog. 6:e1000798.
62. J Fan HZ Bass JL Fahey 1993 Elevated IFN-gamma and decreased IL-2 gene expression are associated with HIV infection J Immunol 151 5031 5040 1:CAS:528:DyaK2cXivFWqsg%3D%3D 8409454
63. Pett SL, Kelleher AD, Emery S. Role of interleukin-2 in patients with HIV infection. Drugs. 70:1115-1130.
64. Weiss L et al. In vivo expansion of naive and activated CD4+ CD25+ FOXP3+ regulatory T cell populations in interleukin-2-treated HIV patients. Proc Natl Acad Sci USA. 107:10632-10637.
65. Owen RE et al. HIV+ elite controllers have low HIV-specific T-cell activation yet maintain strong, polyfunctional T-cell responses. AIDS. 24:1095-1105.
66. S Kannanganat, et al. 2007 Human immunodeficiency virus type 1 controllers but not noncontrollers maintain CD4 T cells coexpressing three cytokines J Virol 81 12071 12076 1:CAS:528:DC%2BD2sXht1ais7%2FN 10.1128/JVI.01261-07 17728221 (Pubitemid 47623838)
67. C Mettling, et al. 2008 Galphai protein-dependant extracellular signal-regulated kinase-1/2 activation is required for HIV-1 reverse transcription AIDS 22 1569 1576 1:CAS:528:DC%2BD1cXpt1Wisrc%3D 10.1097/QAD.0b013e32830abdaf 18670215
68. B Hemonnot, et al. 2004 The host cell MAP kinase ERK-2 regulates viral assembly and release by phosphorylating the p6gag protein of HIV-1 J Biol Chem 279 32426 32434 1:CAS:528:DC%2BD2cXmtVChsb0%3D 10.1074/jbc.M313137200 15155723 (Pubitemid 39014697)
69. X Yang D Gabuzda 1999 Regulation of human immunodeficiency virus type 1 infectivity by the ERK mitogen-activated protein kinase signaling pathway J Virol 73 3460 3466 1:CAS:528:DyaK1MXhvFynu7c%3D 10074203
70. V Witte, et al. 2008 Induction of HIV transcription by Nef involves Lck activation and protein kinase C theta raft recruitment leading to activation of ERK1/2 but not NF kappa B J Immunol 181 8425 8432 1:CAS:528:DC%2BD1cXhsVCktr7L 19050260
71. JA Schrager V Der Minassian JW Marsh 2002 HIV Nef increases T cell ERK MAP kinase activity J Biol Chem 277 6137 6142 1:CAS:528:DC%2BD38XhvFyrtb0%3D 10.1074/jbc.M107322200 11726657 (Pubitemid 34968402)
72. W Popik PM Pitha 1996 Binding of human immunodeficiency virus type 1 to CD4 induces association of Lck and Raf-1 and activates Raf-1 by a Ras-independent pathway Mol Cell Biol 16 6532 6541 1:CAS:528:DyaK28XmsVSjsLk%3D 8887682
73. W Popik JE Hesselgesser PM Pitha 1998 Binding of human immunodeficiency virus type 1 to CD4 and CXCR4 receptors differentially regulates expression of inflammatory genes and activates the MEK/ERK signaling pathway J Virol 72 6406 6413 1:CAS:528:DyaK1cXks1equ7g%3D 9658081
74. N Yoshizuka Y Yoshizuka-Chadani V Krishnan SL Zeichner 2005 Human immunodeficiency virus type 1 Vpr-dependent cell cycle arrest through a mitogen-activated protein kinase signal transduction pathway J Virol 79 11366 11381 1:CAS:528:DC%2BD2MXps1Glt7Y%3D 10.1128/JVI.79.17.11366-11381.2005 16103188 (Pubitemid 41170678)
75. Snyder A et al. HIV-1 viral protein r induces ERK and caspase-8-dependent apoptosis in renal tubular epithelial cells. AIDS. 24:1107-1119.
76. Q Leng G Borkow Z Bentwich 2002 Attenuated signaling associated with immune activation in HIV-1-infected individuals Biochem Biophys Res Commun 298 464 467 1:CAS:528:DC%2BD38XotFSnsrs%3D 10.1016/S0006-291X(02)02460-9 12408974 (Pubitemid 35333680)
77. EJ Duh WJ Maury TM Folks AS Fauci AB Rabson 1989 Tumor necrosis factor alpha activates human immunodeficiency virus type 1 through induction of nuclear factor binding to the NF-kappa B sites in the long terminal repeat Proc Natl Acad Sci USA 86 5974 5978 1:CAS:528:DyaL1MXltFemtrs%3D 10.1073/pnas.86.15.5974 2762307
78. C Veiopoulou, et al. 2004 IL-2 and IL-10 production by human CD4+ T cells is differentially regulated by p38: mode of stimulation-dependent regulation of IL-2 Neuroimmunomodulation 11 199 208 1:CAS:528:DC%2BD2cXlsFCjsLs%3D 10.1159/000078437 15249725 (Pubitemid 38916091)
79. M Saraiva, et al. 2009 Interleukin-10 production by Th1 cells requires interleukin-12-induced STAT4 transcription factor and ERK MAP kinase activation by high antigen dose Immunity 31 209 219 1:CAS:528:DC%2BD1MXhtFOgsL7P 10.1016/j.immuni.2009.05.012 19646904