Rap1 and SPA-1 in hematologic malignancy.
Rap1 is a member of the Ras family of GTPases and, depending on the cellular context, has an important role in the regulation of proliferation or cell adhesion. In lymphohematopoietic tissues, SPA-1 is a principal Rap1 GTPase-activating protein. Mice that are deficient for the SPA-1 gene develop age-dependent progression of T-cell immunodeficiency followed by a spectrum of late onset myeloproliferative disorders, mimicking human chronic myeloid leukemia. Recent studies reveal that deregulated Rap1 activation in SPA-1-deficient mice causes enhanced expansion of the bone marrow hematopoietic progenitors, but induces progressive unresponsiveness or anergy in T cells. Rap1 and its regulator, SPA-1, could, therefore, provide unique molecular targets for the control of human hematologic malignancy.
Department of Immunology and Cell Biology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan.
Kohei
K
Kometani
Daisuke
D
Ishida
Masakazu
M
Hattori
Nagahiro
N
Minato
D000818:Animals; D017635:Clonal Anergy; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000502:physiology*; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism*
D020690:GTPase-Activating Proteins; D009687:Nuclear Proteins; C091108:Sipa1 protein, mouse; D020827:rap1 GTP-Binding Proteins