Evidence map›Paper›PMID 11909938›Full record

ArticleMolecular and cellular biology2002

SRC catalytic but not scaffolding function is needed for integrin-regulated tyrosine phosphorylation, cell migration, and cell spreading.

Leslie A Cary, Richard A Klinghoffer, Christoph Sachsenmaier, Jonathan A Cooper

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
6.8field-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

61 citing papers in PubMed, 143 citations in OpenAlex.

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  11. Cortical Actin Dynamics in Endothelial Permeability.Current topics in membranes · 2018
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1 more citing papers are in PubMed but not listed here.

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

4 authors at 1 institution in 3 countries.

Leslie A CaryDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. lcary@fhcrc.org
Richard A Klinghoffer
Christoph Sachsenmaier
Jonathan A Cooper
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa · ZA

Funding

SRC FAMILY KINASES AND CELL GROWTH REGULATIONR37CA041072 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI COOPER, JONATHAN A. · 1999 to 2006
$3.3M
SRC FAMILY KINASES AND CELL GROWTH REGULATIONR01CA041072 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI COOPER, JONATHAN A · 1986 to 2011
$2.8M
ROLE OF SRC FAMILY KINASES IN CELL MIGRATIONF32CA088447 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI CARY, LESLIE A · 2000 to 2001
$73k
SIGNAL TRANSDUCTION VIA RECEPTOR TYROSINE KINASESR01CA054786 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI COOPER, JONATHAN A. · 1991 to 1999
–
NCI NIH HHS CA41072NCI NIH HHS CA54786NCI NIH HHS CA88447-02NCI NIH HHS F32 CA088447NCI NIH HHS R01 CA041072NCI NIH HHS R37 CA041072
6 · The paper itself

Abstract

Src family kinases (SFKs) are crucial for signaling through a variety of cell surface receptors, including integrins. There is evidence that integrin activation induces focal adhesion kinase (FAK) autophosphorylation at Y397 and that Src binds to and is activated by FAK to carry out subsequent phosphorylation events. However, it has also been suggested that Src functions as a scaffolding molecule through its SH2 and SH3 domains and that its kinase activity is not necessary. To examine the role of SFKs in integrin signaling, we have expressed various Src molecules in fibroblasts lacking other SFKs. In cells plated on fibronectin, FAK could indeed autophosphorylate at Y397 independently of Src but with lower efficiency than when Src was present. This step was promoted by kinase-inactive Src, but Src kinase activity was required for full rescue. Src kinase activity was also required for phosphorylation of additional sites on FAK and for other integrin-directed functions, including cell migration and spreading on fibronectin. In contrast, Src mutations in the SH2 or SH3 domain greatly reduced binding to FAK, Cas, and paxillin but had little effect on tyrosine phosphorylation or biological assays. Furthermore, our indirect evidence indicates that Src kinase activity does not need to be regulated to promote cell migration and FAK phosphorylation. Although Src clearly plays important roles in integrin signaling, it was not concentrated in focal adhesions. These results indicate that the primary role of Src in integrin signaling is as a kinase. Indirect models for Src function are proposed.

Indexed as

3T3 CellsAnimalsCatalysisCell AdhesionCell LineCell MovementFocal Adhesion Kinase 1Focal Adhesion Protein-Tyrosine KinasesHumansIntegrinsMiceMice, KnockoutModels, BiologicalMutationPhosphorylationProtein-Tyrosine KinasesFocal Adhesion Kinase 1Focal Adhesion Protein-Tyrosine KinasesFYN protein, humanFyn protein, mouseIntegrinsProtein-Tyrosine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-fynProto-Oncogene Proteins c-yesPTK2 protein, humanPtk2 protein, mousesrc-Family KinasesTyrosineYES1 protein, humanYes1 protein, mouse

Identifiers

PMID11909938
PMCPMC133722
OpenAlexW2126015832

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.