Spa-1 (Sipa1) and Rap signaling in leukemia and cancer metastasis.
Although Rap GTPases of the Ras family remained enigmatic for years, extensive studies in this decade have revealed diverse functions of Rap in the control of cell proliferation, differentiation, survival, adhesion, and movement. With the use of genetic engineering strategies, we have uncovered essential roles of Rap signaling in normal lymphohematopoietic cell development as well as its crucial involvement in the development of a wide spectrum of leukemia in manners highly dependent on the contexts of cell lineages. Incidentally, recent results also indicate an important role of Spa-1, a Rap GTPase-activating protein, in invasion and metastasis in human cancers. While it is unlikely that Rap can function as a classic oncogene by itself, like Ras, emerging findings unveil crucial involvements of Rap GTPases in the distinct aspects of malignancy, including leukemia genesis and cancer metastasis.
Minato
Nagahiro
N
Department of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. minato@imm.med.kyoto-u.ac.jp
Hattori
Masakazu
M
D000818:Animals; D019070:Cell Lineage; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D006801:Humans; D007938:Leukemia / Q000209:etiology*; D008214:Lymphocytes / Q000502:physiology; D051379:Mice; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins; D015398:Signal Transduction / Q000502:physiology*; D020668:rap GTP-Binding Proteins / Q000378:metabolism*
D020690:GTPase-Activating Proteins; D009687:Nuclear Proteins; C490403:SIPA1 protein, human; D020668:rap GTP-Binding Proteins