We showed previously that the spleen tyrosine kinase Syk is expressed by mammary epithelial cells and that it suppresses malignant growth of breast cancer cells. The exact molecular mechanism of its tumor-suppressive activity remains, however, to be identified. Here, we show that Syk colocalizes and copurifies with the centrosomal component ;-tubulin and exhibits a catalytic activity within the centrosomes. Moreover, its centrosomal localization depends on its intact kinase activity. Centrosomal Syk expression is persistent in interphase but promptly drops during mitosis, obviously resulting from its ubiquitinylation and proteasomal degradation. Conversely, unrestrained exogenous expression of a fluorescently tagged Discosoma sp. red fluorescent protein (DsRed)-Syk chimera engenders abnormal cell division and cell death. Transient DsRed-Syk overexpression triggers an abrupt cell death lacking hallmarks of classic apoptosis but reminiscent of mitotic catastrophe. Surviving stable DsRed-Syktransfected cells exhibit multipolar mitotic spindles and contain multiple abnormally sized nuclei and supernumerary centrosomes, revealing anomalous cell division. Taken together, these results show that Syk is a novel centrosomal kinase that negatively affects cell division. Its expression is strictly controlled in a spatiotemporal manner, and centrosomal Syk levels need to decline to allow customary progression of mitosis. (Cancer Res 2005; 65(23): 10872-80)
PET imaging studies using 5-HT 1A receptor radiotracers show a decreased density of this receptor in hippocampi of patients with Alzheimer's disease (AD) at advanced stages. However, current 5-HT 1A receptor radiopharmaceuticals used in neuroimaging are antagonists, thought to bind to 5-HT 1A receptors in different functional states (i.e., both the one which displays high affinity for agonists and is thought to mediate receptor activation, as well as the state which has low affinity for agonists).Comparing the PET imaging obtained using an agonist radiotracer, which binds selectively to functional receptors, with the PET imaging obtained using an antagonist radiotracer would therefore provide original information on 5-HT 1A receptor impairment during AD. Quantitative autoradiography using [
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