NDLI: 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

Content Provider	PubMed Central
Author	Eckmann, Lars Rudolf, Marco T. Ptasznik, Andrzej Schultz, Carsten Jiang, Tao Wolfson, Nora Tsien, Roger Joshua, Fierer Shears, Stephen B. Kagnoff, Martin F. Traynor-kaplan, Alexis E.
Copyright Year	1997
Abstract	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.
Starting Page	14456
File Format	PDF
ISSN	10916490
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	26
Volume Number	94
Language	English
Publisher	The National Academy of Sciences of the USA
Publisher Date	1997-12-23
Access Restriction	Open
Rights Holder	The National Academy of Sciences of the USA
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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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.

L-myo-inositol 1,4,5,6-tetrakisphosphate (3-hydroxy)kinase.

L-myo-inositol 1,4,5,6-tetrakisphosphate is present in both mammalian and avian cells.

Synthesis of D-myo-inositol 3,4,5,6- and 1,4,5,6-tetrakisphosphate analogues and their membrane-permeant derivatives

myo-Inositol 3,4,5,6-Tetrakisphosphate Inhibits an Apical Calcium-activated Chloride Conductance in Polarized Monolayers of a Cystic Fibrosis Cell Line

A biologic function for an "orphan" messenger: D-myo-inositol 3,4,5,6-tetrakisphosphate selectively blocks epithelial calcium-activated chloride channels.

Diphospho-myo-inositol phosphates from Dictyostelium identified as D-6-diphospho-myo-inositol pentakisphosphate and D-5,6-bisdiphospho-myo-inositol tetrakisphosphate.

Product-precursor relationships amongst inositol polyphosphates. Incorporation of [32P]Pi into myo-inositol 1,3,4,6-tetrakisphosphate, myo-inositol 1,3,4,5-tetrakisphosphate, myo-inositol 3,4,5,6-tetrakisphosphate and myo-inositol 1,3,4,5,6-pentakisphosphate in intact avian erythrocytes.

Identification of Multiple Phosphoinositide-specific Phospholipases D as New Regulatory Enzymes for Phosphatidylinositol 3,4,5-Trisphosphate

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

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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.

L-myo-inositol 1,4,5,6-tetrakisphosphate (3-hydroxy)kinase.

L-myo-inositol 1,4,5,6-tetrakisphosphate is present in both mammalian and avian cells.

Synthesis of D-myo-inositol 3,4,5,6- and 1,4,5,6-tetrakisphosphate analogues and their membrane-permeant derivatives

myo-Inositol 3,4,5,6-Tetrakisphosphate Inhibits an Apical Calcium-activated Chloride Conductance in Polarized Monolayers of a Cystic Fibrosis Cell Line

A biologic function for an "orphan" messenger: D-myo-inositol 3,4,5,6-tetrakisphosphate selectively blocks epithelial calcium-activated chloride channels.

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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