BAX activation is initiated at a novel interaction site

BAX is a pro-apoptotic protein of the BCL-2 family that is stationed in the cytosol until activated by a diversity of stress stimuli to induce cell death. Anti-apoptotic proteins such as BCL-2 counteract BAX-mediated cell death. Although an interaction site that confers survival functionality has been defined for anti-apoptotic proteins, an activation site has not been identified for BAX, rendering its explicit trigger mechanism unknown. We previously developed stabilized alpha-helix of BCL-2 domains (SAHBs) that directly initiate BAX-mediated mitochondrial apoptosis. Here we demonstrate by NMR analysis that BIM SAHB binds BAX at an interaction site that is distinct from the canonical binding groove characterized for anti-apoptotic proteins. The specificity of the human BIM-SAHB-BAX interaction is highlighted by point mutagenesis that disrupts functional activity, confirming that BAX activation is initiated at this novel structural location. Thus, we have now defined a BAX interaction site for direct activation, establishing a new target for therapeutic modulation of apoptosis.     

通过镍(II)-硫键和碘离子基元反应有理合成碘-二硫醇盐桥联的双核镍-镍配合物

本文报道由于碘离子对不稳定的Ni(II)-S(芳基硫醇盐)键的亲核作用,使得Fe(CO)412和Ni(SR)2(dppe(SR=芳基硫醇盐)之间的反应生成NiI2(dppe).含碘和二芳基硫醇盐离子桥联的Ni-Ni双核配合物[(dppe)Ni(μ-I)(μ-pdt)Ni(dppe)]I和[(dppe)Ni(μ-I)(μ-edt)Ni(dppe)]I可方便地由[NiI2(dppe)]和[Ni(pdt)(dppe)]或[Ni(edt)(dppe)]在二氯甲烷的溶液中的反应制得;该类反应可认为是由于硫醇盐离子基团中S-供体上的孤对电子对Ni-I键的进攻所致.另一方面,我们观察到[FeCp(CO)2I]和[Ni(pdt)(dppe)]或[Ni(edt)(dppe)]在二氯甲烷中的反应极其缓慢;但当向上述反应体系中加入NH4PF6进行复分解置换后,源于碘离子和Ni(II)-S键的作用同样可得到含碘与二芳基硫醇盐离子桥联的Ni-Ni双核配合物[(dppe)Ni(μ-I)(μ-pdt)Ni(dppe)]PF6和 [(dppe)Ni(μ-I)(μ-edt)Ni(dppe)]PF6.实验结果说明在本文所讨认的镍(II)-硫醇盐离子-膦配合物中,Ni(II)-S键的反应活性随桥联的第二金属离子和不同的碘离子基元而改变.     

Central nervous system control of mucous gland secretion from frog skin

Summary Surface electrical stimulation of the diencephalic roof of the frog,Rana berlandieri forreri, brain initiates integumental mucous gland secretion which is abolished by pithing.This study was supported, in part, by U.S. Public Health Service grant AM-16282.     

Running activity of ovarian tumorigenic mice

Résumé Les ovaires de souris C3B6F1, génotypeW ^xW^v développent des adénomes tubulaires à l'âge de 7 mois. Dans l'essai du tread wheel l'activité spontanée de ces animaux était plus petite que celle des contrôles.     

Ecto-protein kinase activity on the external surface of neural cells

ATP is secreted in association with neurotransmitters at certain synapses and neuromuscular junctions. Extracellular ATP is known to exert potent effects on the activity of cells in the nervous system, where it can act as a neurotransmitter or as a modulator regulating the activity of other neurohormones. We have suggested that such modulation may involve the activity of extracellular protein phosphorylation systems. It is well known that intracellular protein kinases are important in the regulation of various neuronal functions, but protein kinases which use extracellular ATP to phosphorylate proteins localized at the external surface of the plasma membrane (ecto-protein kinases) have not been demonstrated in neuronal cells. Here we present direct evidence for the existence of an ecto-protein kinase and demonstrate endogenous substrates for its activity at the surface of intact neural cells. The phosphorylation of one of these surface proteins is selectively stimulated during cell depolarization. In addition, neuronal cell adhesion molecules (N-CAMs) appear to be among the substrates of ecto-protein kinase activity. These results suggest a role for surface protein phosphorylation in regulating specific functions of developing and mature neurones.