A PDZ-kinase allosteric relay mediates Par complex regulator exchange.

Elizabeth Vargas, Rhiannon R Penkert, Kenneth E Prehoda

Abstract read

In one paragraph

Article in The Journal of biological chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it

0cells of the map it votes in

1citing papers in PubMed

–field-weighted citation impact

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

1 citing paper in PubMed.

A PAR6-aPKC-LGL structure reveals how LGL antagonizes aPKC.Nature structural & molecular biology · 2025
Article

4 · The record

Corrections and comments

Update of
A PDZ-kinase allosteric relay mediates Par complex regulator exchange.2024

5 · Who and what money

Authors and funding

3 authors.

Elizabeth VargasDepartment of Chemistry and Biochemistry, Institute of Molecular Biology, 1229 University of Oregon, Eugene, Oregon, USA.

Rhiannon R PenkertDepartment of Chemistry and Biochemistry, Institute of Molecular Biology, 1229 University of Oregon, Eugene, Oregon, USA.

Kenneth E PrehodaDepartment of Chemistry and Biochemistry, Institute of Molecular Biology, 1229 University of Oregon, Eugene, Oregon, USA. Electronic address: prehoda@uoregon.edu.

Funding

DEVELOPMENTAL BIOLOGY TRAINING PROGRAMT32HD007348 · NICHD · UNIVERSITY OF OREGON · PI Chris Q Doe, KRYN STANKUNAS · 1989 to 2026

$6.8M

Molecular mechanisms that regulate polarity and spindle orientation in animals - admin supplement to purchase Zeiss Airyscan detector upgradeR35GM127092 · NIGMS · UNIVERSITY OF OREGON · PI Kenneth E Prehoda · 2018 to 2026

$3.6M

NICHD NIH HHS T32 HD007348NIGMS NIH HHS R35 GM127092

6 · The paper itself

Abstract

The Par complex polarizes the plasma membrane of diverse animal cells using the catalytic activity of atypical PKC (aPKC) to pattern substrates. Two upstream regulators of the Par complex, Cdc42 and Par-3, bind separately to the complex to influence its activity in different ways. Each regulator binds a distinct member of the complex, Cdc42 to Par-6 and Par-3 to aPKC, making it unclear how they influence one another's binding. Here, we report the discovery that Par-3 binding to aPKC is regulated by aPKC autoinhibition and link this regulation to Cdc42 and Par-3 exchange. The Par-6 PDZ domain activates aPKC binding to Par-3 via a novel interaction with the aPKC kinase domain. Cdc42 and Par-3 have opposite effects on the Par-6 PDZ-aPKC kinase interaction: while the Par-6 kinase domain interaction competes with Cdc42 binding to the complex, Par-3 binding is enhanced by the interaction. The differential effect of Par-3 and Cdc42 on the Par-6 PDZ interaction with the aPKC kinase domain forms an allosteric relay that connects their binding sites and is responsible for the negative cooperativity that underlies Par complex polarization and activity.

Indexed as

Adaptor Proteins, Signal Transducingcdc42 GTP-Binding ProteinMembrane ProteinsProtein Kinase CAllosteric RegulationAnimalsCell Cycle ProteinsHEK293 CellsHumansPDZ DomainsProtein BindingAdaptor Proteins, Signal Transducingcdc42 GTP-Binding ProteinCDC42 protein, humanCell Cycle ProteinsMembrane ProteinsPARD3 protein, humanPKC-3 proteinProtein Kinase Callosterycell polarityPar complexPDZ domainprotein kinase

Identifiers

PMID39706275

DOI10.1016/j.jbc.2024.108097

PMCPMC11774777

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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.