Evidence map›Paper›PMID 25981199›Full record

ArticleScientific reports2015

The cytosolic tail of the tumor marker protein Trop2--a structural switch triggered by phosphorylation.

Miha Pavšič, Gregor Ilc, Tilen Vidmar, Janez Plavec, Brigita Lenarčič

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 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
0.2field-weighted citation impact, top 45% 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, 27 citations in OpenAlex.

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  11. Entropy-Enthalpy Compensations Fold Proteins in Precise Ways.International journal of molecular sciences · 2021
    Article
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  13. ACS omega · 2020
    Article
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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

5 authors at 1 institution in 1 country.

Miha PavšičDepartment of Chemistry and Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia.
Gregor Ilc1] Slovenian NMR Centre, National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana, Slovenia [2] EN-FIST Centre of Excellence, Dunajska 156, SI-1000 Ljubljana, Slovenia.
Tilen VidmarDepartment of Chemistry and Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia.
Janez Plavec1] Department of Chemistry and Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia [2] Slovenian NMR Centre, National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana, Slovenia [3] EN-FIST Centre of Excellence, Dunajska 156, SI-1000 Ljubljana, Slovenia.
Brigita Lenarčič1] Department of Chemistry and Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia [2] J. Stefan Institute, Department of Biochemistry, Molecular and Structural Biology, Jamova 39, SI-1000 Ljubljana, Slovenia.
University of Ljubljana · SI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Trop2 is a transmembrane signaling glycoprotein upregulated in stem and carcinoma cells. Proliferation-enhancing signaling involves regulated intramembrane proteolytic release of a short cytoplasmic fragment, which is later engaged in a cytosolic signaling complex. We propose that Trop2 function is modulated by phosphorylation of a specific serine residue within this cytosolic region (Ser303), and by proximity effects exerted on the cytosolic tail by Trop2 dimerization. Structural characterization of both the transmembrane (Trop2TM) and cytosolic regions (Trop2IC) support this hypothesis, and shows that the central region of Trop2IC forms an α-helix. Comparison of NMR structures of non-phosphorylated and phosphorylated forms suggest that phosphorylation of Trop2IC triggers salt bridge reshuffling, resulting in significant conformational changes including ordering of the C-terminal tail. In addition, we demonstrate that the cytosolic regions of two Trop2 subunits can be brought into close proximity via transmembrane part dimerization. Finally, we show that Ser303-phosphorylation significantly affects the structure and accessibility of functionally important regions of the cytosolic tail. These observed structural features of Trop2 at the membrane-cytosol interface could be important for regulation of Trop2 signaling activity.

Indexed as

Protein Interaction Domains and MotifsAmino Acid SequenceAntigens, NeoplasmCell Adhesion MoleculesHumansMagnetic Resonance SpectroscopyModels, MolecularMolecular Dynamics SimulationMolecular Sequence DataPhosphorylationProtein ConformationProtein MultimerizationProtein Structure, SecondaryProtein SubunitsSequence AlignmentSignal TransductionAntigens, NeoplasmCell Adhesion MoleculesProtein SubunitsTACSTD2 protein, human

Identifiers

PMID25981199
PMCPMC4434849
OpenAlexW1543107147

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.