IMMUNE NETWORK

The Korean Association of Immunobiologists (대한면역학회)
권호 표지
DOI QR코드

DOI QR Code

Rap Signaling in Normal Lymphocyte Development and Leukemia Genesis

  • Minato, Nagahiro (Department of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University)
  • Received : 2009.03.11
  • Accepted : 2009.03.18
  • Published : 2009.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

Although Rap GTPases of the Ras family remained enigmatic for years, extensive studies in this decade have revealed diverse functions of Rap signaling in the control of cell proliferation, differentiation, survival, adhesion, and movement. With the use of gene-engineered mice, we have uncovered essential roles of endogenous Rap signaling in normal lymphocyte development of both T- and B-lineage cells. Deregulation of Rap signaling, on the other hand, results in the development of characteristic leukemia in manners highly dependent on the contexts of cell lineages. These results highlight crucial roles of Rap signaling in the physiology and pathology of lymphocyte development.

Keywords

References

  1. Pizon V, Chardin P, Lerosey I, Olofsson B, Tavitian A: Human cDNAs rap1 and rap2 homologous to the Drosophila gene Dras3 encode proteins closely related to ras in the 'effector' region. Oncogene 3;201-214, 1988
  2. Bos JL, de Rooij J, Reedquist KA: Rap1 signalling: adhering to new models. Nat Rev Mol Cell Biol 2;369-377, 2001 https://doi.org/10.1038/35073073
  3. Hattori M, Minato N: Rap1 GTPase: functions, regulation, and malignancy. J Biochem 134;479-484, 2003 https://doi.org/10.1093/jb/mvg180
  4. Sasagawa S, Ozaki Y, Fujita K, Kuroda S: Prediction and validation of the distinct dynamics of transient and sustained ERK activation. Nat Cell Biol 7;365-373, 2005 https://doi.org/10.1038/ncb1233
  5. Minato N, Kometani K, Hattori M: Regulation of immune responses and hematopoiesis by the Rap1 signal. Adv Immunol 93;229-264, 2007 https://doi.org/10.1016/S0065-2776(06)93006-5
  6. Tsukamoto N, Hattori M, Yang H, Bos JL, Minato N: Rap1 GTPase-activating protein SPA-1 negatively regulates cell adhesion. J Biol Chem 274;18463-18469, 1999 https://doi.org/10.1074/jbc.274.26.18463
  7. Katagiri K, Hattori M, Minato N, Irie S, Takatsu K, Kinashi T: Rap1 is a potent activation signal for leukocyte function-associated antigen 1 distinct from protein kinase C and phosphatidylinositol-3-OH kinase. Mol Cell Biol 20;1956-1969, 2000 https://doi.org/10.1128/MCB.20.6.1956-1969.2000
  8. Bos JL: Linking Rap to cell adhesion. Curr Opin Cell Biol 17;123-128, 2005 https://doi.org/10.1016/j.ceb.2005.02.009
  9. Katagiri K, Maeda A, Shimonaka M, Kinashi T: RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1. Nat Immunol 4;741-748, 2003 https://doi.org/10.1038/ni950
  10. Duchniewicz M, Zemojtel T, Kolanczyk M, Grossmann S, Scheele JS, Zwartkruis FJ: Rap1A-deficient T and B cells show impaired integrin-mediated cell adhesion. Mol Cell Biol 26;643-653, 2006 https://doi.org/10.1128/MCB.26.2.643-653.2006
  11. Chen Y, Yu M, Podd A, Wen R, Chrzanowska-Wodnicka M, White GC, Wang D: A critical role of Rap1b in B-cell trafficking and marginal zone B-cell development. Blood 111;4627-4636, 2008 https://doi.org/10.1182/blood-2007-12-128140
  12. Dupuy AG, L'Hoste S, Cherfils J, Camonis J, Gaudriault G, de Gunzburg J: Novel Rap1 dominant-negative mutants interfere selectively with C3G and Epac. Oncogene 24;4509-4520, 2005 https://doi.org/10.1038/sj.onc.1208647
  13. Kometani K, Moriyama M, Nakashima Y, Katayama Y, Wang S-F, Saito T, Hattori M, Minato N: Essential role of Rap signal in pre-TCR-mediated $\beta$-selection checkpoint in alphabeta T cell development. Blood 112;4565-4573, 2008 https://doi.org/10.1182/blood-2008-06-164517
  14. Ciofani M, Schmitt TM, Ciofani A, Michie AM, Cuburu N, Aublin A, Maryanski JL, Z\acute{u}\tilde{n}iga-Pflücker JC: Obligatory role for cooperative signaling by pre-TCR and Notch during thymocyte differentiation. J Immunol 172;5230-5239, 2004 https://doi.org/10.4049/jimmunol.172.9.5230
  15. Maillard I, Tu L, Sambandam A, Yashiro-Ohtani Y, Millholland J, Keeshan K, Shestova O, Xu L, Bhandoola A, Pear WS: The requirement for Notch signaling at the betaselection checkpoint in vivo is absolute and independent of the pre-T cell receptor. J Exp Med 203;2239-2245, 2006 https://doi.org/10.1084/jem.20061020
  16. Seet CS, Brumbaugh RL, Kee BL: Early B cell factor promotes B lymphopoiesis with reduced interleukin 7 responsiveness in the absence of E2A. J Exp Med 199; 1689-1700, 2004 https://doi.org/10.1084/jem.20032202
  17. Quong MW, Martensson A, Langerak AW, Rivera RR, Nemazee D, Murre C: Receptor editing and marginal zone B cell development are regulated by the helix-loop-helix protein, E2A. J Exp Med 199;1101-1112, 2004 https://doi.org/10.1084/jem.20031180
  18. Ishida D, Kometani K, Yang H, Kakugawa K, Masuda K, Iwai K, Suzuki M, Itohara S, Nakahata T, Hiai H, Kawamoto H, Hattori M, Minato N: Myeloproliferative stem cell disorders by deregulated Rap1 activation in SPA-1-deficient mice. Cancer Cell 4;55-65, 2003 https://doi.org/10.1016/S1535-6108(03)00163-6
  19. Kurachi H, Wada Y, Tsukamoto N, Maeda M, Kubota H, Hattori M, Iwai K, Minato N: Human SPA-1 gene product selectively expressed in lymphoid tissues is a specific GTPase-activating protein for Rap1 and Rap2. Segregate expression profiles from a rap1GAP gene product. J Biol Chem 272;8081-28088, 1997
  20. Wang SF, Aoki M, Nakashima Y, Shinozuka Y, Tanaka H, Taniwaki M, Hattori M, Minato N: Development of Notchdependent T-cell leukemia by deregulated Rap1 signaling. Blood 111;2878-2886, 2008 https://doi.org/10.1182/blood-2007-07-103119
  21. Grabher C, von Boehmer H, Look AT: Notch 1 activation in the molecular pathogenesis of T-cell acute lymphoblastic leukaemia. Nat Rev Cancer 6;347-359, 2006 https://doi.org/10.1038/nrc1880
  22. Weng AP, Ferrando AA, Lee W, Morris JP 4th, Silverman LB, Sanchez-Irizarry C, Blacklow SC, Look AT, Aster JC: Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science 306;269-271, 2004 https://doi.org/10.1126/science.1102160
  23. Dumortier A, Jeannet R, Kirstetter P, Kleinmann E, Sellars M, dos Santos NR, Thibault C, Barths J, Ghysdael J, Punt JA, Kastner P, Chan S: Notch activation is an early and critical event during T-Cell leukemogenesis in Ikaros-deficient mice. Mol Cell Biol 26;209-220, 2006 https://doi.org/10.1128/MCB.26.1.209-220.2006
  24. Lin YW, Nichols RA, Letterio JJ, Aplan PD: Notch1 mutations are important for leukemic transformation in murine models of precursor-T leukemia/lymphoma. Blood 107;2540-2543, 2006 https://doi.org/10.1182/blood-2005-07-3013
  25. O'Neil J, Calvo J, McKenna K, Krishanamoorthy V, Aster JC, Bassing CH, Alt FW, Kelliher M, Look AT: Activating Notch1 mutations in mouse models of T-ALL. Blood 107;781-785, 2006 https://doi.org/10.1182/blood-2005-06-2553
  26. O'Neil J, Grim J, Strack P, Rao S, Tibbitts D, Winter C, Hardwick J, Welcker M, Meijerink JP, Pieters R, Draetta G, Sears R, Clurman BE, Look AT: FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to gamma-secretase inhibitors. J Exp Med 204;1813-1824, 2007 https://doi.org/10.1084/jem.20070876
  27. Ishida D, Su L, Tamura A, Katayama Y, Wang S-F, Taniwaki M, Hamazaki Y, Hattori M, Minato N: Rap1 signal controls B cell receptor repertoire and generation of self-reactive B1a cells. Immunity 24;417-427, 2006 https://doi.org/10.1016/j.immuni.2006.02.007
  28. Minato N, Hattori M: Spa-1 (Sipa-1) and Rap signaling in leukemia and cancer metastasis. Cancer Sci 100;17-23, 2009 https://doi.org/10.1111/j.1349-7006.2008.01011.x