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Inositol 1,4,5-trisphosphate ([InsP.sub.3]) receptors ([InsP.sub.3]Rs) are channels responsible for calcium release from the endoplasmic reticulum (ER). We show that the anti-apoptotic protein Bcl-2 (either wild type or selectively localized to the ER) significantly inhibited [InsP.sub.3]-mediated calcium release and elevation of cytosolic calcium in WEHI7.2 T cells. This inhibition was due to an effect of Bcl-2 at the level of [InsP.sub.3]Rs because responses to both anti-CD3 antibody and a cell-permeant [InsP.sub.3] ester were decreased. Bcl-2 inhibited the extent of calcium release from the ER of permeabilized WEHI7.2 cells, even at saturating concentrations of [InsP.sub.3], without decreasing luminal calcium concentration. Furthermore, Bcl-2 reduced the open probability of purified [InsP.sub.3]Rs reconstituted into lipid bilayers. Bcl-2 and [InsP.sub.3]Rs were detected together in macromolecular complexes by coimmunoprecipitation and blue native gel electrophoresis. We suggest that this functional interaction of Bcl-2 with [InsP.sub.3]Rs inhibits [lnsP.sub.3]R activation and thereby regulates [InsP.sub.3]-induced calcium release from the ER.

The synthesis and photophysical study of a series of solution-processible phosphorescent iridium complexes are described. These covalently bound materials show improvements in efficiency over simple blends and will form the basis of future investigations into energy-transfer processes occurring in light-emitting diodes.

Protein kinase B (PKB) is activated in response to phosphoinositide 3-kinases and their lipid products phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)[P.sub.3]] and PtdIns(3,4)[P.sub.2] in the signaling pathways used by a wide variety of growth factors, antigens, and inflammatory stimuli. PKB is a direct target of these lipids, but this regulation is complex. The lipids can bind to the pleckstrin homologous domain of PKB, causing its translocation to the membrane, and also enable upstream, [Thr.sup.308]-directed kinases to phosphorylate and activate PKB. Four isoforms of these PKB kinases were purified from sheep brain. They bound PtdIns(3,4,5)[P.sub.3] and associated with lipid vesicles containing it. These kinases contain an [NH.sub.2]-terminal catalytic domain and a COOH-terminal pleckstrin homologous domain, and their heterologous expression augments receptor activation of PKB, which suggests they are the primary signal transducers that enable PtdIns(3,4,5)[P.sub.3] or PtdIns(3,4)[P.sub.2] to activate PKB and hence to control signaling pathways regulating cell survival, glucose uptake, and glycogen metabolism., Phosphoinositide 3-kinases (PI3Ks) are a diverse family of enzymes capable of 3-phosphorylating inositol phospholipids(1). One subfamily can he activated by receptors through various signal transduction mechanisms. These enzymes phosphorylate PtdIns, [...]

The key steps involved in the enantioselective synthesis of (+)-laurencin (1), achieved in 27 stages from (R)-malic acid (20), involved methylenation of lactone (49), intramolecular hydrosilation of enol ether (14) and a carbon homologation of diol (13). This gave a key ethyl substituted cyclic ether (59). 49 was obtained through Claisen ring expansion, alpha-hydroxylation and Yamaguchi lactonization. The synthesis of 1 was completed with an elaboration of the (E)-pentenynyl side chain and introduction of bromine.

Poly(p-phenylenevinylene) (PPV) based conjugated polymers have characteristic portions of high and low HOMO-LUMO gap energy which is chemically and electronically regulated using molecular engineering techniques. Two conjugated poly(arylenevinylene) related to PPV and MEH-PPV are used as light-emitting compounds in electroluminescent devices. Methoxy withdrawing groups in precursor polymers heated to a temperature of 220 degrees celsius effect the synthesis of these conjugated polymers. Partially conjugated polymers characterized by regions of high and low HOMO-LUMO gap energy is obtained during thermal treatment of precursor polymers. These partially conjugated polymers are 30 times more efficient than PPV in exhibiting electroluminescence.