Rap1 and SPA-1 in hematologic malignancy.

Kohei Kometani; Daisuke Ishida; Masakazu Hattori; Nagahiro Minato

doi:10.1016/j.molmed.2004.06.004

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Rap1 and SPA-1 in hematologic malignancy.

Kohei Kometani·Daisuke Ishida·Masakazu Hattori·Nagahiro Minato

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Abstract

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.

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Animals Clonal Anergy GTPase-Activating Proteins Hematologic Neoplasms Humans Mice Mice, Knockout Nuclear Proteins T-Lymphocytes rap1 GTP-Binding Proteins Journal Article Review

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Kohei Kometani, Daisuke Ishida, Masakazu Hattori, Nagahiro Minato. 2004. Rap1 and SPA-1 in hematologic malignancy.. https://doi.org/10.1016/j.molmed.2004.06.004

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