Evidence map›Paper›PMID 26460884›Full record

ArticleBiochemistry2015

G protein-coupled receptors directly bind filamin A with high affinity and promote filamin phosphorylation.

Kalyan C Tirupula, Sujay S Ithychanda, Maradumane L Mohan, Sathyamangla V Naga Prasad, Jun Qin, Sadashiva S Karnik

Open access · greenAbstract read
In one paragraph

Article in Biochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.4field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 32 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Kalyan C TirupulaDepartment of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic , Cleveland, Ohio 44195, United States.
Sujay S IthychandaDepartment of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic , Cleveland, Ohio 44195, United States.
Maradumane L MohanDepartment of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic , Cleveland, Ohio 44195, United States.
Sathyamangla V Naga PrasadDepartment of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic , Cleveland, Ohio 44195, United States.
Jun QinDepartment of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic , Cleveland, Ohio 44195, United States.
Sadashiva S KarnikDepartment of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic , Cleveland, Ohio 44195, United States.
Cleveland Clinic Lerner College of Medicine · US

Funding

NMR Structural Elucidation of Integrin ActivationR01GM062823 · NIGMS · CLEVELAND CLINIC LERNER COM-CWRU · PI QIN, JUN · 2002 to 2018
$5.1M
Molecular Basis of Ang II Receptor FunctionsR01HL057470 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI KARNIK, SADASHIVA S · 1997 to 2013
$4.4M
Novel Regulation of Beta Andregenic Receptor FunctionR01HL089473 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI PRASAD, SATHYAMANGLA V · 2008 to 2017
$3.7M
Regulation of AT1R-signaling and pathology in vessels through microRNAR01HL115964 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI KARNIK, SADASHIVA S · 2012 to 2015
$1.5M
NHLBI NIH HHS HL057470NHLBI NIH HHS HL089473NHLBI NIH HHS R01 HL115964NIGMS NIH HHS GM062823NIGMS NIH HHS R01 GM062823
6 · The paper itself

Abstract

Although interaction of a few G protein-coupled receptors (GPCRs) with Filamin A, a key actin cross-linking and biomechanical signal transducer protein, has been observed, a comprehensive structure-function analysis of this interaction is lacking. Through a systematic sequence-based analysis, we found that a conserved filamin binding motif is present in the cytoplasmic domains of >20% of the 824 GPCRs encoded in the human genome. Direct high-affinity interaction of filamin binding motif peptides of select GPCRs with the Ig domain of Filamin A was confirmed by nuclear magnetic resonance spectroscopy and isothermal titration calorimetric experiments. Engagement of the filamin binding motif with the Filamin A Ig domain induced the phosphorylation of filamin by protein kinase A in vitro. In transfected cells, agonist activation as well as constitutive activation of representative GPCRs dramatically elicited recruitment and phosphorylation of cellular Filamin A, a phenomenon long known to be crucial for regulating the structure and dynamics of the cytoskeleton. Our data suggest a molecular mechanism for direct GPCR-cytoskeleton coupling via filamin. Until now, GPCR signaling to the cytoskeleton was predominantly thought to be indirect, through canonical G protein-mediated signaling cascades involving GTPases, adenylyl cyclases, phospholipases, ion channels, and protein kinases. We propose that the GPCR-induced filamin phosphorylation pathway is a conserved, novel biochemical signaling paradigm.

Indexed as

Amino Acid SequenceBinding SitesCell LineCyclic AMP-Dependent Protein KinasesFilaminsHumansModels, MolecularMolecular Sequence DataPhosphorylationProtein BindingProtein Interaction Domains and MotifsReceptors, G-Protein-CoupledSignal TransductionCyclic AMP-Dependent Protein KinasesFilaminsReceptors, G-Protein-Coupled

Identifiers

PMID26460884
PMCPMC4642222
OpenAlexW2238695690

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.