Evidence map›Paper›PMID 36108633›Full record

ArticleMolecular cell2022

Condensed-phase signaling can expand kinase specificity and respond to macromolecular crowding.

Dajun Sang, Tong Shu, Christian F Pantoja, Alain Ibáñez de Opakua, Markus Zweckstetter, Liam J Holt

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
7.5field-weighted citation impact, top 2% 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

58 citing papers in PubMed, 94 citations in OpenAlex.

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  9. Chemical reviews · 2026
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  15. Activation of WNK1 signaling through Piezo1.Proceedings of the National Academy of Sciences of the United States of America · 2025
    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

6 authors at 2 institutions in 2 countries.

Dajun SangInstitute for Systems Genetics, New York University Langone Medical Center, 435 E 30th Street, New York, NY 10010, USA.
Tong ShuInstitute for Systems Genetics, New York University Langone Medical Center, 435 E 30th Street, New York, NY 10010, USA.
Christian F PantojaGerman Center for Neurodegenerative Diseases (DZNE), Von-Siebold-Str. 3a, 37075 Göttingen, Germany.
Alain Ibáñez de OpakuaGerman Center for Neurodegenerative Diseases (DZNE), Von-Siebold-Str. 3a, 37075 Göttingen, Germany.
Markus ZweckstetterGerman Center for Neurodegenerative Diseases (DZNE), Von-Siebold-Str. 3a, 37075 Göttingen, Germany; Max Planck Institute for Multidisciplinary Sciences, Department of NMR-based Structural Biology, Am Fassberg 11, 37077 Göttingen, Germany. Electronic address: mazw@mpinat.mpg.de.
Liam J HoltInstitute for Systems Genetics, New York University Langone Medical Center, 435 E 30th Street, New York, NY 10010, USA. Electronic address: liam.holt@nyulangone.org.
German Center for Neurodegenerative Diseases · DENYU Langone Health · US

Funding

The Physical Biology of Neurodegeneration in Sporadic Amyotrophic Lateral Sclerosis/Frontotemporal DementiaR01NS127186 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI HOLT, LIAM J, PHATNANI, HEMALI · 2021 to 2025
$8.2M
Cancer under pressure: Mechanisms of adaptation to compressive stressR37CA240765 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI HOLT, LIAM J · 2019 to 2025
$3.2M
Tools to probe the biophysical properties of cellsR01GM132447 · NIGMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI HOLT, LIAM J · 2019 to 2022
$2.1M
NCI NIH HHS R37 CA240765NIGMS NIH HHS R01 GM132447NINDS NIH HHS R01 NS127186
6 · The paper itself

Abstract

Phase separation can concentrate biomolecules and accelerate reactions. However, the mechanisms and principles connecting this mesoscale organization to signaling dynamics are difficult to dissect because of the pleiotropic effects associated with disrupting endogenous condensates. To address this limitation, we engineered new phosphorylation reactions within synthetic condensates. We generally found increased activity and broadened kinase specificity. Phosphorylation dynamics within condensates were rapid and could drive cell-cycle-dependent localization changes. High client concentration within condensates was important but not the main factor for efficient phosphorylation. Rather, the availability of many excess client-binding sites together with a flexible scaffold was crucial. Phosphorylation within condensates was also modulated by changes in macromolecular crowding. Finally, the phosphorylation of the Alzheimer's-disease-associated protein Tau by cyclin-dependent kinase 2 was accelerated within condensates. Thus, condensates enable new signaling connections and can create sensors that respond to the biophysical properties of the cytoplasm.

Indexed as

Signal Transductiontau ProteinsCyclin-Dependent Kinase 2CytoplasmHumansMacromolecular SubstancesCyclin-Dependent Kinase 2Macromolecular Substancestau ProteinsAlzheimer’s diseasebiochemistrybiophysicsmacromolecular crowdingmicrorheologyphase separationphosphoregulationsynthetic biologyTau

Identifiers

PMID36108633
PMCPMC10101210
OpenAlexW4295693197

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.