E3KARP (NHE3 kinase a anchoring protein) is necessary for cGMP regulation of NHE3: Demonstration of a plasma membrane signaling complex containing NHE3, E3KARP, and cGMP kinase II

2001 ◽  
Vol 120 (5) ◽  
pp. A85 ◽  
Author(s):  
Bo-Young Cha ◽  
Jae-Hoe Kim ◽  
Hans Hut ◽  
Whaseon Lee Kwon ◽  
Janini Nadarajah ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Signaling Complex ◽  
Anchoring Protein ◽  
Membrane Signaling ◽  
Kinase A

scholarly journals A Small Novel A-Kinase Anchoring Protein (AKAP) That Localizes Specifically Protein Kinase A-Regulatory Subunit I (PKA-RI) to the Plasma Membrane

2012 ◽  
Vol 287 (52) ◽  
pp. 43789-43797 ◽  
Author(s):  
Pepijn P. Burgers ◽  
Yuliang Ma ◽  
Luigi Margarucci ◽  
Mason Mackey ◽  
Marcel A. G. van der Heyden ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Regulatory Subunit ◽  
Anchoring Protein ◽  
Kinase A

Compartmentalization of adenylate cyclase and cAMP signalling

2005 ◽  
Vol 33 (6) ◽  
pp. 1319-1322 ◽  
Author(s):  
D.M.F. Cooper
Keyword(s):  
Plasma Membrane ◽  
Signalling Pathways ◽  
Scaffolding Proteins ◽  
Subcellular Targeting ◽  
Camp Signalling ◽  
Cellular Processes ◽  
Cyclic Nucleotide Gated Channels ◽  
Anchoring Protein ◽  
Raft Domains ◽  
Kinase A

Concepts of cAMP signalling have changed dramatically from the linear cascades of just a few years ago, with the realization that numerous cellular processes affect this motif. These influences include other signalling pathways – most significantly Ca2+, scaffolding proteins (which are themselves variously regulated) to organize the elements of the pathway, and subcellular targeting of components. An obvious implication of this organization is that global measurements of cAMP may trivialize the complexity of the cAMP signals and obscure the regulation of targets. In this presentation, current developments on the targeting and assembly of ACs (adenylate cyclases) and their delivery to selected raft or non-raft domains of the plasma membrane will be discussed, along with the susceptibility of raft-targeted ACs to very discrete modes of increases in the intracellular Ca2+ concentration. Single-cell explorations of cAMP dynamics, as measured with cyclic nucleotide-gated channels, are also described in this paper, particularly as applied to cells in which the composition of AKAP (A-kinase anchoring protein)–PKA (protein kinase A)–PDE (phosphodiesterase) assemblies is probed by RNA interference ablation of defined AKAPs.

scholarly journals Multiple Interactions within the AKAP220 Signaling Complex Contribute to Protein Phosphatase 1 Regulation

2001 ◽  
Vol 276 (15) ◽  
pp. 12128-12134 ◽  
Author(s):  
Robynn V. Schillace ◽  
James W. Voltz ◽  
Alistair T. R. Sim ◽  
Shirish Shenolikar ◽  
John D. Scott
Keyword(s):  
Intermolecular Interactions ◽  
Protein Interactions ◽  
Protein Phosphatase ◽  
Competitive Inhibitor ◽  
Regulatory Subunit ◽  
Protein Protein Interactions ◽  
Signaling Complex ◽  
Activity Measurements ◽  
Anchoring Protein ◽  
Pka Regulatory Subunit

The phosphorylation status of cellular proteins is controlled by the opposing actions of protein kinases and phosphatases. Compartmentalization of these enzymes is critical for spatial and temporal control of these phosphorylation/dephosphorylation events. We previously reported that a 220-kDa A-kinase anchoring protein (AKAP220) coordinates the location of the cAMP-dependent protein kinase (PKA) and the type 1 protein phosphatase catalytic subunit (PP1c) (Schillace, R. V., and Scott, J. D. (1999)Curr. Biol.9, 321–324). We now demonstrate that an AKAP220 fragment is a competitive inhibitor of PP1c activity (Ki= 2.9 ± 0.7 μm). Mapping studies and activity measurements indicate that several protein-protein interactions act synergistically to inhibit PP1. A consensus targeting motif, between residues 1195 and 1198 (Lys-Val-Gln-Phe), binds but does not affect enzyme activity, whereas determinants between residues 1711 and 1901 inhibit the phosphatase. Analysis of truncated PP1c and chimeric PP1/2A catalytic subunits suggests that AKAP220 inhibits the phosphatase in a manner distinct from all known PP1 inhibitors and toxins. Intermolecular interactions within the AKAP220 signaling complex further contribute to PP1 inhibition as addition of the PKA regulatory subunit (RII) enhances phosphatase inhibition. These experiments indicate that regulation of PP1 activity by AKAP220 involves a complex network of intra- and intermolecular interactions.

scholarly journals Inhibition of Tumor Necrosis Factor (TNF) Signal Transduction by the Adenovirus Group C RID Complex Involves Downregulation of Surface Levels of TNF Receptor 1

2004 ◽  
Vol 78 (23) ◽  
pp. 13113-13121 ◽  
Author(s):  
Shawn P. Fessler ◽  
Y. Rebecca Chin ◽  
Marshall S. Horwitz
Keyword(s):  
Plasma Membrane ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tnf Receptor ◽  
Signaling Complex ◽  
Antiviral Responses ◽  
Mechanism Of Inhibition ◽  
Early Transcription ◽  
Necrosis Factor ◽  
Inhibit Tumor Necrosis Factor

ABSTRACT Adenoviruses employ multiple genes to inhibit the host antiviral responses. There is increasing evidence that these immunoregulatory genes may function either during lytic or latent infection. Adenovirus early transcription region 3 (E3) encodes at least seven proteins, five of which block the acquired or innate immune response. Previous findings from this laboratory demonstrated that the E3 proteins 10.4K and 14.5K, which form a complex in the plasma membrane, inhibit tumor necrosis factor (TNF)-induced activation of NF-κB and the synthesis of chemokines. To determine the mechanism of inhibition of these pathways by the adenovirus E3 10.4K/14.5K proteins, we have examined the effects of this viral complex on the inhibition of AP-1 and NF-κB activation by TNF and found a reduction in assembly of the TNF receptor 1 (TNFR1) signaling complex at the plasma membrane accompanied by downregulation of surface levels of TNFR1.

scholarly journals STIM2 targets Orai1/STIM1 to the AKAP79 signaling complex and confers coupling of Ca2+entry with NFAT1 activation

2020 ◽  
Vol 117 (28) ◽  
pp. 16638-16648 ◽  
Author(s):  
Ga-Yeon Son ◽  
Krishna Prasad Subedi ◽  
Hwei Ling Ong ◽  
Lucile Noyer ◽  
Hassan Saadi ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Unique Role ◽  
Signaling Complex ◽  
Contact Sites ◽  
Channel Function

The Orai1 channel is regulated by stromal interaction molecules STIM1 and STIM2 within endoplasmic reticulum (ER)-plasma membrane (PM) contact sites. Ca2+signals generated by Orai1 activate Ca2+-dependent gene expression. When compared with STIM1, STIM2 is a weak activator of Orai1, but it has been suggested to have a unique role in nuclear factor of activated T cells 1 (NFAT1) activation triggered by Orai1-mediated Ca2+entry. In this study, we examined the contribution of STIM2 in NFAT1 activation. We report that STIM2 recruitment of Orai1/STIM1 to ER-PM junctions in response to depletion of ER-Ca2+promotes assembly of the channel with AKAP79 to form a signaling complex that couples Orai1 channel function to the activation of NFAT1. Knockdown of STIM2 expression had relatively little effect on Orai1/STIM1 clustering or local and global [Ca2+]iincreases but significantly attenuated NFAT1 activation and assembly of Orai1 with AKAP79. STIM1ΔK, which lacks the PIP2-binding polybasic domain, was recruited to ER-PM junctions following ER-Ca2+depletion by binding to Orai1 and caused local and global [Ca2+]iincreases comparable to those induced by STIM1 activation of Orai1. However, in contrast to STIM1, STIM1ΔK induced less NFAT1 activation and attenuated the association of Orai1 with STIM2 and AKAP79. Orai1-AKAP79 interaction and NFAT1 activation were recovered by coexpressing STIM2 with STIM1ΔK. Replacing the PIP2-binding domain of STIM1 with that of STIM2 eliminated the requirement of STIM2 for NFAT1 activation. Together, these data demonstrate an important role for STIM2 in coupling Orai1-mediated Ca2+influx to NFAT1 activation.

AQP2 is a substrate for endogenous PP2B activity within an inner medullary AKAP-signaling complex

2001 ◽  
Vol 281 (5) ◽  
pp. F958-F965 ◽  
Author(s):  
Inho Jo ◽  
Donald T. Ward ◽  
Michelle A. Baum ◽  
John D. Scott ◽  
Vincent M. Coghlan ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Regulatory Subunit ◽  
Relative Molecular Mass ◽  
Signaling Complex ◽  
Anchoring Protein ◽  
Pka Regulatory Subunit

We have demonstrated that inner medullary collecting duct (IMCD) heavy endosomes purified from rat kidney IMCD contain the type II protein kinase A (PKA) regulatory subunit (RII), protein phosphatase (PP)2B, PKCζ, and an RII-binding protein (relative molecular mass ∼90 kDa) representing a putative A kinase anchoring protein (AKAP). Affinity chromatography of detergent-solubilized endosomes on cAMP-agarose permits recovery of a protein complex consisting of the 90-kDa AKAP, RII, PP2B, and PKCζ. With the use of small-particle flow cytometry, RII and PKCζ were localized to an identical population of endosomes, suggesting that these proteins are components of an endosomal multiprotein complex.32P-labeled aquaporin-2 (AQP2) present in these PKA-phosphorylated endosomes was dephosphorylated in vitro by either addition of exogenous PP2B or by an endogenous endosomal phosphatase that was inhibited by the PP2B inhibitors EDTA and the cyclophilin-cyclosporin A complex. We conclude that IMCD heavy endosomes possess an AKAP multiprotein-signaling complex similar to that described previously in hippocampal neurons. This signaling complex potentially mediates the phosphorylation of AQP2 to regulate its trafficking into the IMCD apical membrane. In addition, the PP2B component of the AKAP-signaling complex could also dephosphorylate AQP2 in vivo.

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