Recently cDNA encoding the histamine H3 receptor was isolated after 15 years of considerable research. However, several studies have proposed heterogeneity of the H3 receptor. We report here the molecular cloning and ...
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Recently cDNA encoding the histamine H3 receptor was isolated after 15 years of considerable research. However, several studies have proposed heterogeneity of the H3 receptor. We report here the molecular cloning and characterization of a novel type of histamine receptor. A novel orphan G-protein-coupled receptor named GPRv53 was obtained through a search of the human genomic DNA data base and analyzed by rapid amplification of cDNA ends (RACE), GPRv53 possessed the features of biologic amine receptors and had the highest homology with H3 receptor among known G-protein-coupled receptors. Mammalian cells expressing GPRv53 were demonstrated to bind and respond to histamine in a concentration-dependent manner. In functional assays, not only an H3 receptor agonist, R-(alpha)-methylhistamine, but also a H3 receptor antagonist, clobenpropit, and a neuroleptic, clozapine, activated GPRv53-expressing cells. Tissue distribution analysis revealed that expression of GPRv53 is localized in the peripheral blood leukocytes, spleen, thymus, and colon, which was totally different from the H3 receptor, whose expression was restricted to the brain. The discovery of the GPRv53 receptor will open a new phase of research on the physiological role of histamine.
The expression of hormone receptors and their relationship-to cell proliferation in six samples of normal canine mammary tissue, and 11 benign and 10 malignant mammary neoplasms from female dogs were assessed by immun...
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The expression of hormone receptors and their relationship-to cell proliferation in six samples of normal canine mammary tissue, and 11 benign and 10 malignant mammary neoplasms from female dogs were assessed by immunohistochemistry in formalin-fixed paraffin-embedded samples, by using monoclonal antibodies against progesterone and oestrogen receptors, and nuclear antigen Ki-67 (MIB-1). Malignant tumours negative for progesterone receptors proliferated at higher rates than progesterone receptor-positive tumours, suggesting that the progression towards malignancy in spontaneous mammary tumours is accompanied by a decrease in hormonal steroid dependency. Only one malignant tumour was positive for oestrogen receptors.
Crosslinking of immunoreceptor tyrosine-based activation motif (ITAM)-containing receptor complexes on a variety of cells leads to their activation through the sequential triggering of protein tyrosine kinases, Recent...
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Crosslinking of immunoreceptor tyrosine-based activation motif (ITAM)-containing receptor complexes on a variety of cells leads to their activation through the sequential triggering of protein tyrosine kinases, Recently, DAP12 has been identified as an ITAM-bearing signaling molecule that is noncovalently associated with activating isoforms of MHC class I receptors on natural killer cells, In addition to natural killer cells, DAP12 is expressed in peripheral blood monocytes, macrophages, and dendritic cells, suggesting association with other receptors present in these cell types. In the present study, we report the molecular cloning of the myeloid DAP12 associating lectin-l (MDL-1), a DAP12-associating membrane receptor expressed exclusively in monocytes and macrophages, MDL-1 is a type II transmembrane protein belonging to the C type lectin superfamily and contains a charged residue in the transmembrane region that enables it to pair with DAP12, Crosslinking of MDL-1/DAP12 complexes in J774 mouse macrophage cells resulted in calcium mobilization, These findings suggest that signaling,ia MDL-1/DAP12 complexes may constitute a significant activation pathway in myeloid cells.
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