The polyphosphoinositide PtdIns(4,5)P2, best known as a substrate for phospholipase C isozymes, has recently been recognized to be involved in a variety of other cellular processes. The aim of this study was to examine whether the cellular levels of this versatile phospholipid are controlled by tyrosine phosphorylation. The studies were performed in human embryonic kidney (HEK)-293 cells stably...

BACKGROUND The role of organic anion transporting polypeptide 5A1 (OATP5A1) a member of a family of drug transporters that mediate cellular uptake of drugs has not been characterized so far. METHODS Gene expression levels of OATP5A1 in small cell lung cancer (SCLC) cell lines were determined by real-time qPCR and chemosensitivity of HEK-293-SLCO5A1-transfected cells to satraplatin in MTT assa...

Cyclic nucleotide-gated (CNG) channels are the primary targets of light- and odorant-induced signaling in photoreceptors and olfactory sensory neurons. Compartmentalized cyclic nucleotide signaling is necessary to ensure rapid and efficient activation of these nonselective cation channels. However, relatively little is known about the subcellular localization of CNG channels or the mechanisms o...

The purpose of this study was to determine the mechanism of action of SPI-0211 (lubiprostone), a novel bicyclic fatty acid in development for the treatment of bowel dysfunction. Adult rabbit intestine was shown to contain mRNA for ClC-2 using RT-PCR, Northern blot analysis, and in situ hybridization. T84 cells grown to confluence on permeable supports were shown to express ClC-2 channel protein...

The circadian clock is regulated by a transcription/translation negative feedback loop. A key negative regulator of circadian rhythm in mammals is the PER2 (mammalian PERIOD 2) protein. Its daily degradation at the end of the night accompanies de-repression of transcription. CKI (casein kinase I ) has been identified as the kinase that phosphorylates PER2, targeting it for ubiquitin-mediated pr...

The physiological meaning of the coexpression of adenosine A2A receptors and group I metabotropic glutamate receptors in gamma- aminobutyric acid (GABA)ergic striatal neurons is intriguing. Here we provide in vitro and in vivo evidence for a synergism between adenosine and glutamate based on subtype 5 metabotropic glutamate (mGluR5) and adenosine A2A (A2AR) receptor/receptor interactions. Coloc...

Thymus-expressed chemokine (TECK) has been reported to chemoattract dendritic cells, thymocytes, and activated macrophages. Here, we show that TECK is a specific agonist for a human orphan receptor called GPR-9-6. We have determined the cDNA sequence of human GPR-9-6 and cloned the corresponding murine cDNA. Human and murine GPR-9-6 expression is very high in the thymus and low in lymph nodes a...

INTRODUCTION Since the early 1990s, recombinant human clotting factor VIII (rhFVIII) produced in hamster cells has been available for haemophilia A treatment. However, the post-translational modifications of these proteins are not identical to those of native human FVIII, which may lead to immunogenic reactions and the development of inhibitors against rhFVIII. For the first time, rhFVIII produ...