Evidence map›Paper›PMID 25713130›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Multimodular biosensors reveal a novel platform for activation of G proteins by growth factor receptors.

Krishna K Midde, Nicolas Aznar, Melanie B Laederich, Gary S Ma, Maya T Kunkel, Alexandra C Newton, Pradipta Ghosh

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
3.3field-weighted citation impact, top 7% 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

38 citing papers in PubMed, 48 citations in OpenAlex.

  1. Article
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  10. Receptor tyrosine kinases activate heterotrimeric G proteins via phosphorylation within the interdomain cleft of Gαi.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  11. Regulating cellular cyclic adenosine monophosphate: "Sources," "sinks," and now, "tunable valves".Wiley interdisciplinary reviews. Systems biology and medicine · 2020
    Review
  12. Article
  13. DAPLE protein inhibits nucleotide exchange on GαThe Journal of biological chemistry · 2020
    Article
  14. Structural basis for GPCR-independent activation of heterotrimeric Gi proteins.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  15. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Krishna K MiddeDepartments of Medicine and.
Nicolas AznarDepartments of Medicine and.
Melanie B LaederichDepartments of Medicine and.
Gary S MaDepartments of Medicine and.
Maya T KunkelPharmacology and.
Alexandra C NewtonPharmacology and.
Pradipta GhoshDepartments of Medicine and Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093 prghosh@ucsd.edu.
University of California, San Diego · US

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jesse Nodora · 1985 to 2026
$124.9M
Project# 4: INTERACTIONS OF ANCHORING PROTEINS WITH THEIR TARGETSP01DK054441 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TAYLOR, SUSAN S. · 1999 to 2017
$27.3M
U of Calif, San Diego Neuroscience Microscopy ImagingP30NS047101 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G, ZHENG, BINHAI · 2003 to 2022
$9.0M
Training Grant in GastroenterologyT32DK007202 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GHOSH, PRADIPTA · 1985 to 2022
$7.7M
Modulation of G proteins by Growth FactorsR01CA160911 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GHOSH, PRADIPTA · 2013 to 2017
$1.8M
G Protein pathways as Novel Therapeutic and Diagnostic Targets in Liver FibrosisR01DK099226 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GHOSH, PRADIPTA · 2014 to 2016
$698k
NCI NIH HHS P30 CA023100NCI NIH HHS P30 CA23100NCI NIH HHS R01CA16091NCI NIH HHS R01 CA160911NIDDK NIH HHS P01 DK054441NIDDK NIH HHS R01 DK099226NIDDK NIH HHS T32 DK007202NINDS NIH HHS P30 NS047101
6 · The paper itself

Abstract

Environmental cues are transmitted to the interior of the cell via a complex network of signaling hubs. Receptor tyrosine kinases (RTKs) and trimeric G proteins are two such major signaling hubs in eukaryotes. Conventionally, canonical signal transduction via trimeric G proteins is thought to be triggered exclusively by G protein-coupled receptors. Here we used molecular engineering to develop modular fluorescent biosensors that exploit the remarkable specificity of bimolecular recognition, i.e., of both G proteins and RTKs, and reveal the workings of a novel platform for activation of G proteins by RTKs in single living cells. Comprised of the unique modular makeup of guanidine exchange factor Gα-interacting vesicle-associated protein (GIV)/girdin, a guanidine exchange factor that links G proteins to a variety of RTKs, these biosensors provide direct evidence that RTK-GIV-Gαi ternary complexes are formed in living cells and that Gαi is transactivated within minutes after growth factor stimulation at the plasma membrane. Thus, GIV-derived biosensors provide a versatile strategy for visualizing, monitoring, and manipulating the dynamic association of Gαi with RTKs for noncanonical transactivation of G proteins in cells and illuminate a fundamental signaling event regulated by GIV during diverse cellular processes and pathophysiologic states.

Indexed as

GTP-Binding ProteinsReceptor Protein-Tyrosine KinasesReceptors, Growth FactorSignal TransductionAnimalsBiosensing TechniquesChlorocebus aethiopsCOS CellsFluorescence Resonance Energy TransferHumansMicrofilament ProteinsVesicular Transport ProteinsCCDC88A protein, humanGTP-Binding ProteinsMicrofilament ProteinsReceptor Protein-Tyrosine KinasesReceptors, Growth FactorVesicular Transport ProteinsAktcyclic AMPGirdingrowth factor receptor tyrosine kinaseheterotrimeric G proteininvasionPI3-kinase

Identifiers

PMID25713130
PMCPMC4352799
OpenAlexW2014333610

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.