Evidence map›Paper›PMID 34169835›Full record

ArticleeLife2021

A Cas-BCAR3 co-regulatory circuit controls lamellipodia dynamics.

Elizabeth M Steenkiste, Jason D Berndt, Carissa Pilling, Christopher Simpkins, Jonathan A Cooper

Open access · goldAbstract read
In one paragraph

Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.1field-weighted citation impact, top 26% 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

6 citing papers in PubMed, 9 citations in OpenAlex.

  1. Cancers · 2026
    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 2 institutions in 1 country.

Elizabeth M SteenkisteDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States.ORCID 0000-0001-6452-2340
Jason D Berndt *Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States.
Carissa Pilling *Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States.
Christopher SimpkinsDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States.ORCID 0000-0003-3174-6609
Jonathan A CooperDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States.ORCID 0000-0002-8626-7827
University of Washington · USFred Hutch Cancer Center · US

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Marian Esvelt · 1985 to 2026
$296.4M
VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MATTHEW G. VANDER HEIDEN · 1985 to 2026
$93.9M
TRAINING IN MOLECULAR AND CELLULAR BIOLOGYT32GM007270 · NIGMS · UNIVERSITY OF WASHINGTON · PI RAIBLE, DAVID W · 1985 to 2020
$21.0M
Regulation of cell migration and signaling by phosphotyrosine and ubiquitinR01GM109463 · NIGMS · FRED HUTCHINSON CANCER RESEARCH CENTER · PI COOPER, JONATHAN A · 2014 to 2022
$3.0M
NCI NIH HHS P30 CA014051NCI NIH HHS P30 CA015704NIGMS NIH HHS R01 GM109463NIGMS NIH HHS T32 GM007270NIH HHS P30 CA015704NIH HHS R01 GM109463NIH HHS T32 GM007270
6 · The paper itself

Abstract

Integrin adhesion complexes regulate cytoskeletal dynamics during cell migration. Adhesion activates phosphorylation of integrin-associated signaling proteins, including Cas (p130Cas, BCAR1), by Src-family kinases. Cas regulates leading-edge protrusion and migration in cooperation with its binding partner, BCAR3. However, it has been unclear how Cas and BCAR3 cooperate. Here, using normal epithelial cells, we find that BCAR3 localization to integrin adhesions requires Cas. In return, Cas phosphorylation, as well as lamellipodia dynamics and cell migration, requires BCAR3. These functions require the BCAR3 SH2 domain and a specific phosphorylation site, Tyr 117, that is also required for BCAR3 downregulation by the ubiquitin-proteasome system. These findings place BCAR3 in a co-regulatory positive-feedback circuit with Cas, with BCAR3 requiring Cas for localization and Cas requiring BCAR3 for activation and downstream signaling. The use of a single phosphorylation site in BCAR3 for activation and degradation ensures reliable negative feedback by the ubiquitin-proteasome system.

Indexed as

Signal TransductionAdaptor Proteins, Signal TransducingCell AdhesionCell LineCrk-Associated Substrate ProteinEpithelial CellsGuanine Nucleotide Exchange FactorsHumansIntegrinsPhosphorylationPseudopodiasrc Homology DomainsAdaptor Proteins, Signal TransducingBCAR1 protein, humanBCAR3 protein, humanCrk-Associated Substrate ProteinGuanine Nucleotide Exchange FactorsIntegrinscell biologycell migrationhumanphosphorylationphosphotyrosineubiquitination

Identifiers

PMID34169835
PMCPMC8266394
OpenAlexW3174666206

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.