d-myo-Inositol 1,4,5,6-tetrakisphosphate produced in human intestinal epithelial cells in response to Salmonella invasion inhibits phosphoinositide 3-kinase signaling pathways

Several inositol-containing compounds play key roles in receptor-mediated cell signaling events. Here, we describe a function for a specific inositol polyphosphate, d-myo-inositol 1,4,5,6-tetrakisphosphate [Ins(1,4,5,6)P4], that is produced acutely in response to a receptor-independent process. Thus, infection of intestinal epithelial cells with the enteric pathogen Salmonella, but not with other invasive bacteria, induced a multifold increase in Ins(1,4,5,6)P4 levels. To define a specific function of Ins(1,4,5,6)P4, a membrane-permeant, hydrolyzable ester was used to deliver it to the intracellular compartment, where it antagonized epidermal growth factor (EGF)-induced inhibition of calcium-mediated chloride (Cl−) secretion (CaMCS) in intestinal epithelia. This EGF function is likely mediated through a phosphoinositide 3-kinase (PtdIns3K)-dependent mechanism because the EGF effects are abolished by wortmannin, and three different membrane-permeant esters of the PtdIns3K product phosphatidylinositol 3,4,5-trisphosphate mimicked the EGF effect on CaMCS. We further demonstrate that Ins(1,4,5,6)P4 antagonized EGF signaling downstream of PtdIns3K because Ins(1,4,5,6)P4 interfered with the PtdInsP3 effect on CaMCS without affecting PtdIns3K activity. Thus, elevation of Ins(1,4,5,6)P4 in Salmonella-infected epithelia may promote Cl− flux by antagonizing EGF inhibition mediated through PtdIns3K and PtdInsP3.

Cloning and mitochondrial localization of full-length D-AKAP2, a protein kinase A anchoring protein

Differential compartmentalization of signaling molecules in cells and tissues is being recognized as an important mechanism for regulating the specificity of signal transduction pathways. A kinase anchoring proteins (AKAPs) direct the subcellular localization of protein kinase A (PKA) by binding to its regulatory (R) subunits. Dual specific AKAPs (D-AKAPs) interact with both RI and RII. A 372-residue fragment of mouse D-AKAP2 with a 40-residue C-terminal PKA binding region and a putative regulator of G protein signaling (RGS) domain was previously identified by means of a yeast two-hybrid screen. Here, we report the cloning of full-length human D-AKAP2 (662 residues) with an additional putative RGS domain, and the corresponding mouse protein less the first two exons (617 residues). Expression of D-AKAP2 was characterized by using mouse tissue extracts. Full-length D-AKAP2 from various tissues shows different molecular weights, possibly because of alternative splicing or posttranslational modifications. The cloned human gene product has a molecular weight similar to one of the prominent mouse proteins. In vivo association of D-AKAP2 with PKA in mouse brain was demonstrated by using cAMP agarose pull-down assay. Subcellular localization for endogenous mouse, rat, and human D-AKAP2 was determined by immunocytochemistry, immunohistochemistry, and tissue fractionation. D-AKAP2 from all three species is highly enriched in mitochondria. The mitochondrial localization and the presence of RGS domains in D-AKAP2 may have important implications for its function in PKA and G protein signal transduction.

Hid��yat al-murīd lil-sabīl al-ḥamīd li-Shaykh al-Islām al-Ustādh Abī Bakr Muḥammad ibn Abī al-Ḥasan al-Bakrī al-Ṣiddīqī : manuscript, 1887 or 8

Unbound.

L'expédition d'Egypte /

On added t.p.: Septième série.--Format in-80 cavalier ill.

Mémoires du comte Roger de Damas ...

[t. 1] Russie, Valmy et armee de conde Naples (1787-1806).--[t. 2] Vienne de 1806 à 1814, suivis de lettres inédites de Marie-Carolina, reine de Naples, au comte Roger de Damas (1801-1814).

Le Palais-Royal d'après des documents inédits (1629-1900) : ouvrage illustré de planches hors texte, eaux-fortes, héliotypies, fac-similés d'aquarelles et de nombreuses gravures dans le texte /

Includes index.

Breve saggio d'iconografia classica di San Nicola da Tolentino /

Mode of access: Internet.

Memoires de M. Joly ... pour servir d'éclaircissement [et] de suite aux memoires de M. le C. de Retz : tome premier.

Mode of access: Internet.

Primicias euangelicas do padre D. Rafael Bluteau clerigo Regular Theatino da diuina Prouidecia ...

Mode of access: Internet.

Octava parte de comedias verdaderas del celebre poeta español D. Pedro Calderón de la Barca ... que corregidas por sus originales publicó Don Juan de Vera Tassis y Villarroel ...

Contiene: La cisma de Inglaterra (pp. 1-45) ; Las manos blancas no ofenden (pp. 46-104) ; Los cabellos de Absalón (pp. 105-155) ; No siempre lo peor es cierto (pp. 156-200) ; Las cadenas del demonio (pp. 201-239) ; Los tres afectos de amor, piedad, desmayo y valor (pp. 240-287) ; La vanda y la flor (pp. 288-330) ; Con quien vengo, vengo (pp. 331-380) ; Guárdate de la agua mansa (pp. 381-430) ; El alcayde de sí mismo (pp. 431-473) ; Luis Pérez el Gallego (pp. 474-516) ; Antes que todo es mi dama (pp. 517-570)

Saint François d'Assise.

At head of title: R. Boutet de Monvel.

Appendix a La flor del moral ó Explicacion de la Doctrina Christiana ... /

Mode of access: Internet.