Forskolin-inducible cAMP pathway negatively regulates T-cell proliferation by uncoupling the interleukin-2 receptor complex

Journal of Biological Chemistry

Volumn 288, Issue 10, 2013, Pages 7137-7146

  Rodriguez, Georgialina ^a   Ross, Jeremy A ^a   Nagy, Zsuzsanna S ^a   Kirken, Robert A ^a  

^a UNIVERSITY OF TEXAS AT EL PASO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ELEVATED LEVEL; HUMAN T CELLS; INTERLEUKIN-2; MULTIPLE LEVELS; RECEPTOR COMPLEX; THERAPEUTIC POTENTIALS;

CELL PROLIFERATION; CROSSTALK;

T-CELLS;

ADENYLATE KINASE; CYCLIC AMP; CYCLIC AMP DEPENDENT PROTEIN KINASE; FORSKOLIN; INTERLEUKIN 2; INTERLEUKIN 2 RECEPTOR; INTERLEUKIN 2 RECEPTOR BETA; INTERLEUKIN 2 RECEPTOR GAMMA; JANUS KINASE 3; SERINE; STAT5 PROTEIN; TYROSINE;

ARTICLE; CELL CYCLE REGULATION; CELLULAR IMMUNITY; CONTROLLED STUDY; DNA BINDING; EMBRYO; ENZYME ACTIVATION; ENZYME ASSAY; ENZYME MECHANISM; GENE EXPRESSION; HUMAN; HUMAN CELL; IN VITRO STUDY; INHIBITION KINETICS; LYMPHOCYTE PROLIFERATION; MOLECULAR INTERACTION; MOLECULAR MODEL; PHARMACOLOGICAL BLOCKING; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN TRANSPORT; SIGNAL TRANSDUCTION;

1-METHYL-3-ISOBUTYLXANTHINE; BLOTTING, WESTERN; CELL CYCLE PROTEINS; CELL LINE, TUMOR; CELL PROLIFERATION; CYCLIC AMP; CYCLIC AMP-DEPENDENT PROTEIN KINASES; ENZYME ACTIVATION; FORSKOLIN; GENE EXPRESSION; HEK293 CELLS; HUMANS; INTERLEUKIN-2; INTERLEUKIN-2 RECEPTOR BETA SUBUNIT; JANUS KINASE 3; PHOSPHORYLATION; PROTEIN BINDING; PROTEIN SUBUNITS; PROTEIN TRANSPORT; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; STAT5 TRANSCRIPTION FACTOR; T-LYMPHOCYTES;

EID: 84874839720     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M112.408765     Document Type: Article

References (61)

1. Leonard, W. J. (1996) STATs and cytokine specificity. Nat. Med. 2, 968-969 (Pubitemid 26306828)
2. Weaver, A. M., and Silva, C. M. (2006) Modulation of signal transducer and activator of transcription 5b activity in breast cancer cells by mutation of tyrosines within the transactivation domain. Mol. Endocrinol. 20, 2392-2405 (Pubitemid 44496409)
3. Lin, J. X., Mietz, J., Modi, W. S., John, S., and Leonard, W. J. (1996) Cloning of human Stat5B. Reconstitution of interleukin-2-induced Stat5A and Stat5B DNA binding activity in COS-7 cells. J. Biol. Chem. 271, 10738-10744 (Pubitemid 26145810)
4. Lin, J. X., and Leonard, W. J. (2000) The role of Stat5a and Stat5b in signaling by IL-2 family cytokines. Oncogene 19, 2566-2576 (Pubitemid 30339212)
5. Park, S. H., Yamashita, H., Rui, H., and Waxman, D. J. (2001) Serine phosphorylation of GH-activated signal transducer and activator of transcription 5a (STAT5a) and STAT5b: Impact on STAT5 transcriptional activity. Mol. Endocrinol. 15, 2157-2171 (Pubitemid 33141135)
6. Xue, H. H., Fink, D. W., Jr., Zhang, X., Qin, J., Turck, C. W., and Leonard, W. J. (2002) Serine phosphorylation of Stat5 proteins in lymphocytes stimulated with IL-2. Int. Immunol. 14, 1263-1271 (Pubitemid 35331423)
7. Weaver, A. M., and Silva, C. M. (2007) S731 in the transactivation domain modulates STAT5b activity. Biochem. Biophys. Res. Commun. 362, 1026-1030 (Pubitemid 47390677)
8. Mitra, A., Ross, J. A., Rodriguez, G., Nagy, Z. S., Wilson, H. L., and Kirken, R. A. (2012) Signal transducer and activator of transcription 5b (Stat5b) serine 193 is a novel cytokine-induced phospho-regulatory site that is constitutively activated in primary hematopoietic malignancies. J. Biol. Chem. 287, 16596-16608
9. Ross, J. A., Nagy, Z. S., Cheng, H., Stepkowski, S. M., and Kirken, R. A. (2007) Regulation of T cell homeostasis by JAKs and STATs. Arch. Immunol. Ther. Exp. 55, 231-245 (Pubitemid 47262712)
10. Taskén, K., and Aandahl, E. M. (2004) Localized effects of cAMP mediated by distinct routes of protein kinase A. Physiol. Rev. 84, 137-167 (Pubitemid 38049878)
11. Vandamme, J., Castermans, D., and Thevelein, J. M. (2012) Molecular mechanisms of feedback inhibition of protein kinase A on intracellular cAMP accumulation. Cell Signal. 24, 1610-1618
12. Houslay, M. D. (2010) Underpinning compartmentalised cAMP signalling through targeted cAMP breakdown. Trends Biochem. Sci. 35, 91-100
13. Biel, M., and Michalakis, S. (2009) Cyclic nucleotide-gated channels. Handb. Exp. Pharmacol. 191, 111-136
14. Grandoch, M., Roscioni, S. S., and Schmidt, M. (2010) The role of Epac proteins, novel cAMP mediators, in the regulation of immune, lung and neuronal function. Br. J. Pharmacol. 159, 265-284
15. Mosenden, R., and Taskén, K. (2011) Cyclic AMP-mediated immune regulation-overview of mechanisms of action in T cells. Cell Signal. 23, 1009-1016
16. Zhang, H., Conrad, D. M., Butler, J. J., Zhao, C., Blay, J., and Hoskin, D. W. (2004) Adenosine acts through A2 receptors to inhibit IL-2-induced tyrosine phosphorylation of STAT5 in T lymphocytes: Role of cyclic adenosine 3',5'-monophosphate and phosphatases. J. Immunol. 173, 932-944 (Pubitemid 38924266)
17. Elliott, L., Brooks, W., and Roszman, T. (1992) Inhibition of anti-CD3 monoclonal antibody-induced T-cell proliferation by dexamethasone, isoproterenol, or prostaglandin E2 either alone or in combination. Cell Mol. Neurobiol. 12, 411-427
18. Ekholm, D., Mulloy, J. C., Gao, G., Degerman, E., Franchini, G., and Manganiello, V. C. (1999) Cyclic nucleotide phosphodiesterases (PDE) 3 and 4 in normal, malignant, and HTLV-I transformed human lymphocytes. Biochem. Pharmacol 58, 935-950 (Pubitemid 29361460)
19. Bury, T. B., Corhay, J. L., and Radermecker, M. F. (1992) Histamine-induced inhibition of neutrophil chemotaxis and T-lymphocyte proliferation in man. Allergy 47, 624-629 (Pubitemid 23010735)
20. Essayan, D. M., Huang, S. K., Undem, B. J., Kagey-Sobotka, A., and Lichtenstein, L. M. (1994) Modulation of antigen-and mitogen-induced proliferative responses of peripheral blood mononuclear cells by nonselective and isozyme selective cyclic nucleotide phosphodiesterase inhibitors. J. Immunol. 153, 3408-3416
21. Huang, S., Apasov, S., Koshiba, M., and Sitkovsky, M. (1997) Role of A2a extracellular adenosine receptor-mediated signaling in adenosine-mediated inhibition of T-cell activation and expansion. Blood 90, 1600-1610 (Pubitemid 27355433)
22. Lingk, D. S., Chan, M. A., and Gelfand, E. W. (1990) Increased cyclic adenosine monophosphate levels block progression but not initiation of human T cell proliferation. J. Immunol. 145, 449-455 (Pubitemid 20252347)
23. Maca, R. D. (1984) The effects of cyclic nucleotides on the proliferation of cultured human T-lymphocytes. Immunopharmacology 8, 53-60 (Pubitemid 16182953)
24. Zhu, J., Huang, H., Guo, L., Stonehouse, T., Watson, C. J., Hu-Li, J., and Paul, W. E. (2000) Transient inhibition of interleukin 4 signaling by T cell receptor ligation. J. Exp. Med. 192, 1125-1134
25. Lee, I. H., Li, W. P., Hisert, K. B., and Ivashkiv, L. B. (1999) Inhibition of interleukin 2 signaling and signal transducer and activator of transcription (STAT)5 activation during T cell receptor-mediated feedback inhibition of T cell expansion. J. Exp. Med. 190, 1263-1274 (Pubitemid 29522210)
26. Miyoshi, I., Kubonishi, I., Yoshimoto, S., and Shiraishi, Y. (1981) A T-cell line derived from normal human cord leukocytes by co-culturing with human leukemic T-cells. Gann 72, 978-981 (Pubitemid 12172471)
27. Kirken, R. A., Erwin, R. A., Taub, D., Murphy, W. J., Behbod, F., Wang, L., Pericle, F., and Farrar, W. L. (1999) Tyrphostin AG-490 inhibits cytokinemediated JAK3/STAT5a/b signal transduction and cellular proliferation of antigen-activated human T cells. J. Leukoc Biol. 65, 891-899 (Pubitemid 29279542)
28. Hori, T., Uchiyama, T., Tsudo, M., Umadome, H., Ohno, H., Fukuhara, S., Kita, K., and Uchino, H. (1987) Establishment of an interleukin 2-dependent human T cell line from a patient with T cell chronic lymphocytic leukemia who is not infected with human T cell leukemia/lymphoma virus. Blood 70, 1069-1072 (Pubitemid 18022384)
29. Malabarba, M. G., Rui, H., Deutsch, H. H., Chung, J., Kalthoff, F. S., Farrar, W. L., and Kirken, R. A. (1996) Biochem. J. 319 (Pt 3), 865-872
30. Behbod, F., Nagy, Z. S., Stepkowski, S. M., Karras, J., Johnson, C. R., Jarvis, W. D., and Kirken, R. A. (2003) Specific inhibition of Stat5a/b promotes apoptosis of IL-2-responsive primary and tumor-derived lymphoid cells. J. Immunol. 171, 3919-3927 (Pubitemid 37238663)
31. Cheng, H., Ross, J. A., Frost, J. A., and Kirken, R. A. (2008) Phosphorylation of human Jak3 at tyrosines 904 and 939 positively regulates its activity. Mol. Cell Biol. 28, 2271-2282 (Pubitemid 351429973)
32. Ross, J. A., Cheng, H., Nagy, Z. S., Frost, J. A., and Kirken, R. A. (2010) Protein phosphatase 2A regulates interleukin-2 receptor complex formation and JAK3/STAT5 activation. J. Biol. Chem. 285, 3582-3591
33. Ross, J. A., Nagy, Z. S., and Kirken, R. A. (2008) The PHB1/2 phosphocomplex is required for mitochondrial homeostasis and survival of human T cells. J. Biol. Chem. 283, 4699-4713
34. Nagy, Z. S., Rui, H., Stepkowski, S. M., Karras, J., and Kirken, R. A. (2006) A preferential role for STAT5, not constitutively active STAT3, in promoting survival of a human lymphoid tumor. J. Immunol. 177, 5032-5040 (Pubitemid 44527573)
35. Bartik, M. M., Brooks, W. H., and Roszman, T. L. (1993) Modulation of T cell proliferation by stimulation of the ?-adrenergic receptor: Lack of correlation between inhibition of T cell proliferation and cAMP accumulation. Cell Immunol. 148, 408-421 (Pubitemid 23162633)
36. Mullen, P. (2004) PARP cleavage as a means of assessing apoptosis. Methods Mol. Med. 88, 171-181
37. Zambon, A. C., Zhang, L., Minovitsky, S., Kanter, J. R., Prabhakar, S., Salomonis, N., Vranizan, K., Dubchak, I., Conklin, B. R., and Insel, P. A. (2005) Gene expression patterns define key transcriptional events in cellcycle regulation by cAMP and protein kinase A. Proc. Natl. Acad. Sci. U.S.A. 102, 8561-8566 (Pubitemid 40862775)
38. Stork, P. J., and Schmitt, J. M. (2002) Crosstalk between cAMP and MAP kinase signaling in the regulation of cell proliferation. Trends Cell Biol. 12, 258-266 (Pubitemid 34634174)
39. Moriggl, R., Topham, D. J., Teglund, S., Sexl, V., McKay, C., Wang, D., Hoffmeyer, A., van Deursen, J., Sangster, M. Y., Bunting, K. D., Grosveld, G. C., and Ihle, J. N. (1999) Stat5 is required for IL-2-induced cell cycle progression of peripheral T cells. Immunity 10, 249-259 (Pubitemid 29115630)
40. Nagy, Z. S., LeBaron, M. J., Ross, J. A., Mitra, A., Rui, H., and Kirken, R. A. (2009) STAT5 regulation of BCL10 parallels constitutive NFkB activation in lymphoid tumor cells. Mol. Cancer 8, 67
41. Gouilleux, F., Wakao, H., Mundt, M., and Groner, B. (1994) Prolactin induces phosphorylation of Tyr694 of Stat5 (MGF), a prerequisite for DNA binding and induction of transcription. EMBO J. 13, 4361-4369 (Pubitemid 24295208)
42. Zhou, Y. J., Hanson, E. P., Chen, Y. Q., Magnuson, K., Chen, M., Swann, P. G., Wange, R. L., Changelian, P. S., and O'Shea, J. J. (1997) Distinct tyrosine phosphorylation sites in JAK3 kinase domain positively and negatively regulate its enzymatic activity. Proc. Natl. Acad. Sci. U.S.A. 94, 13850-13855 (Pubitemid 28009673)
43. Ellery, J. M., and Nicholls, P. J. (2002) Alternate signalling pathways from the interleukin-2 receptor. Cytokine Growth Factor Rev. 13, 27-40 (Pubitemid 34436960)
44. Kirken, R. A., Malabarba, M. G., Xu, J., DaSilva, L., Erwin, R. A., Liu, X., Hennighausen, L., Rui, H., and Farrar, W. L. (1997) Two discrete regions of interleukin-2 (IL2) receptor β independently mediate IL2 activation of a PD98059/rapamycin/wortmannin-insensitive Stat5a/b serine kinase. J. Biol. Chem. 272, 15459-15465 (Pubitemid 27255572)
45. Nagy, Z. S., Wang, Y., Erwin-Cohen, R. A., Aradi, J., Monia, B., Wang, L. H., Stepkowski, S. M., Rui, H., and Kirken, R. A. (2002) Interleukin-2 family cytokines stimulate phosphorylation of the Pro-Ser-Pro motif of Stat5 transcription factors in human T cells: Resistance to suppression of multiple serine kinase pathways. J. Leukoc. Biol. 72, 819-828 (Pubitemid 36277854)
46. Decker, T., and Kovarik, P. (2000) Serine phosphorylation of STATs. Oncogene 19, 2628-2637 (Pubitemid 30339219)
47. Boyman, O., and Sprent, J. (2012) The role of interleukin-2 during homeostasis and activation of the immune system. Nat. Rev. Immunol. 12, 180-190
48. Chai, S. K., Nichols, G. L., and Rothman, P. (1997) Constitutive activation of JAKs and STATs in BCR-Abl-expressing cell lines and peripheral blood cells derived from leukemic patients. J. Immunol. 159, 4720-4728 (Pubitemid 127471006)
49. Weber-Nordt, R. M., Egen, C., Wehinger, J., Ludwig, W., Gouilleux-Gruart, V., Mertelsmann, R., and Finke, J. (1996) Constitutive activation of STAT proteins in primary lymphoid and myeloid leukemia cells and in Epstein-Barr virus (EBV)-related lymphoma cell lines. Blood 88, 809-816 (Pubitemid 26333300)
50. Takemoto, S., Mulloy, J. C., Cereseto, A., Migone, T. S., Patel, B. K., Matsuoka, M., Yamaguchi, K., Takatsuki, K., Kamihira, S., White, J. D., Leonard, W. J., Waldmann, T., and Franchini, G. (1997) Proliferation of adult T cell leukemia/lymphoma cells is associated with the constitutive activation of JAK/STAT proteins. Proc. Natl. Acad. Sci. U.S.A. 94, 13897-13902 (Pubitemid 28009681)
51. Gerdes, J., Schwab, U., Lemke, H., and Stein, H. (1983) Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int. J. Cancer 31, 13-20 (Pubitemid 13179545)
52. Cone, R. E., Cochrane, R., Lingenheld, E. G., and Clark, R. B. (1996) Elevation of intracellular cyclic AMP induces an anergic-like state in Th1 clones. Cell Immunol. 173, 246-251 (Pubitemid 26381403)
53. Kirken, R. A., Rui, H., Malabarba, M. G., Howard, O. M., Kawamura, M., O'Shea, J. J., and Farrar, W. L. (1995) Activation of JAK3, but not JAK1, is critical for IL-2-induced proliferation and STAT5 recruitment by a COOH-terminal region of the IL-2 receptorβ-chain. Cytokine 7, 689-700
54. Taskén, K., and Stokka, A. J. (2006) The molecular machinery for cAMPdependent immunomodulation in T-cells. Biochem. Soc. Trans. 34, 476-479 (Pubitemid 44230740)
55. Sadana, R., and Dessauer, C. W. (2009) Physiological roles for G proteinregulated adenylyl cyclase isoforms: Insights from knockout and overexpression studies. Neurosignals 17, 5-22
56. Ivashkiv, L. B. (2008) A signal-switch hypothesis for cross-regulation of cytokine and TLR signalling pathways. Nat. Rev. Immunol. 8, 816-822
57. Kammer, G. M., Boehm, C. A., Rudolph, S. A., and Schultz, L. A. (1988) Mobility of the human T lymphocyte surface molecules CD3, CD4, and CD8: Regulation by a cAMP-dependent pathway. Proc. Natl. Acad. Sci. U.S.A. 85, 792-796 (Pubitemid 18073917)
58. Bopp, T., Becker, C., Klein, M., Klein-Hessling, S., Palmetshofer, A., Serfling, E., Heib, V., Becker, M., Kubach, J., Schmitt, S., Stoll, S., Schild, H., Staege, M. S., Stassen, M., Jonuleit, H., and Schmitt, E. (2007) Cyclic adenosine monophosphate is a key component of regulatory T cell-mediated suppression. J. Exp. Med. 204, 1303-1310 (Pubitemid 46919868)
59. Nokta, M. A., and Pollard, R. B. (1992) Human immunodeficiency virus replication: Modulation by cellular levels of cAMP. AIDS Res. Hum. Retroviruses 8, 1255-1261
60. Nokta, M., and Pollard, R. (1991) Human immunodeficiency virus infection: Association with altered intracellular levels of cAMP and cGMP in MT-4 cells. Virology 181, 211-217
61. Antonysamy, M. A., Moticka, E. J., and Ramkumar, V. (1995) Adenosine acts as an endogenous modulator of IL-2-dependent proliferation of cytotoxic T lymphocytes. J. Immunol. 155, 2813-2821