NDLI: Distinct Protein Kinase A Anchoring Proteins Direct Prostaglandin E2 Modulation of Toll-like Receptor Signaling in Alveolar Macrophages*

Content Provider	PubMed Central
Author	Kim, Sang-hoon Henrique, Serezani Carlos Okunishi, Katsuhide Zaslona, Zbigniew Aronoff, David M. Marc, Peters-golden
Abstract	Toll-like receptors (TLRs) direct a proinflammatory program in macrophages. One mediator whose generation is induced by TLR ligation is prostaglandin E2 (PGE2), which is well known to increase intracellular cAMP upon G protein-coupled receptor ligation. How PGE2/cAMP shapes the nascent TLR response and the mechanisms by which it acts remain poorly understood. Here we explored PGE2/cAMP regulation of NO production in primary rat alveolar macrophages stimulated with the TLR4 ligand LPS. Endogenous PGE2 synthesis accounted for nearly half of the increment in NO production in response to LPS. The enhancing effect of PGE2 on LPS-stimulated NO was mediated via cAMP, generated mainly upon ligation of the E prostanoid 2 receptor and acting via protein kinase A (PKA) rather than via the exchange protein activated by cAMP. Isoenzyme-selective cAMP agonists and peptide disruptors of protein kinase A anchoring proteins (AKAPs) implicated PKA regulatory subunit type I (RI) interacting with an AKAP in this process. Gene knockdown of potential RI-interacting AKAPs expressed in alveolar macrophages revealed that AKAP10 was required for PGE2 potentiation of LPS-induced NO synthesis. AKAP10 also mediated PGE2 potentiation of the expression of cytokines IL-10 and IL-6, whereas PGE2 suppression of TNF-α was mediated by AKAP8-anchored PKA-RII. Our data illustrate the pleiotropic manner in which G protein-coupled receptor-derived cAMP signaling can influence TLR responses in primary macrophages and suggest that AKAP10 may coordinate increases in gene expression.
Related Links	http://dx.doi.org/10.1074/jbc.m110.187815
Ending Page	8883
Page Count	9
Starting Page	8875
File Format	PDF
ISSN	00219258
e-ISSN	1083351X
Journal	The Journal of Biological Chemistry
Issue Number	11
Volume Number	286
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2011-03-18
Access Restriction	Open
Rights Holder	American Society for Biochemistry and Molecular Biology
Subject Keyword	Cell Biology Biochemistry Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Distinct Protein Kinase A Anchoring Proteins Direct Prostaglandin E2 Modulation of Toll-like Receptor Signaling in Alveolar Macrophages

Plasmin Overcomes Resistance to Prostaglandin E2 in Fibrotic Lung Fibroblasts by Reorganizing Protein Kinase A Signaling

Protein Kinase C and Toll-Like Receptor Signaling

Prostaglandin E2 restrains macrophage maturation via E prostanoid receptor 2/protein kinase A signaling

Direct Modulation of Heterotrimeric G Protein-coupled Signaling by a Receptor Kinase Complex

Plasmin Overcomes Resistance to Prostaglandin E2 in Fibrotic Lung Fibroblasts by Reorganizing Protein Kinase A Signaling*

G-protein-coupled receptor-associated A-kinase anchoring proteins AKAP5 and AKAP12: differential signaling to MAPK and GPCR recycling

Effects of prostaglandin E2 on the subcellular localization of Epac-1 and Rap1 proteins during Fcγ receptor mediated phagocytosis in alveolar macrophages

Endocytosis of Mycobacterium tuberculosis heat shock protein 60 is required to induce interleukin-10 production in macrophages.

Distinct Protein Kinase A Anchoring Proteins Direct Prostaglandin E2 Modulation of Toll-like Receptor Signaling in Alveolar Macrophages*

Similar Documents

Distinct Protein Kinase A Anchoring Proteins Direct Prostaglandin E2 Modulation of Toll-like Receptor Signaling in Alveolar Macrophages

Plasmin Overcomes Resistance to Prostaglandin E2 in Fibrotic Lung Fibroblasts by Reorganizing Protein Kinase A Signaling

Protein Kinase C and Toll-Like Receptor Signaling

Prostaglandin E2 restrains macrophage maturation via E prostanoid receptor 2/protein kinase A signaling

Direct Modulation of Heterotrimeric G Protein-coupled Signaling by a Receptor Kinase Complex

Plasmin Overcomes Resistance to Prostaglandin E2 in Fibrotic Lung Fibroblasts by Reorganizing Protein Kinase A Signaling*

G-protein-coupled receptor-associated A-kinase anchoring proteins AKAP5 and AKAP12: differential signaling to MAPK and GPCR recycling

Effects of prostaglandin E2 on the subcellular localization of Epac-1 and Rap1 proteins during Fcγ receptor mediated phagocytosis in alveolar macrophages

Endocytosis of Mycobacterium tuberculosis heat shock protein 60 is required to induce interleukin-10 production in macrophages.

Distinct Protein Kinase A Anchoring Proteins Direct Prostaglandin E2 Modulation of Toll-like Receptor Signaling in Alveolar Macrophages*