Evidence map›Paper›PMID 19574212›Full record

ArticleThe Journal of biological chemistry2009

Increased protein stability of FGF1 can compensate for its reduced affinity for heparin.

Malgorzata Zakrzewska, Antoni Wiedlocha, Anna Szlachcic, Daniel Krowarsch, Jacek Otlewski, Sjur Olsnes

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

31 citing papers in PubMed, 60 citations in OpenAlex.

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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 3 institutions in 3 countries.

Malgorzata ZakrzewskaCentre for Cancer Biomedicine, University of Oslo, and Department of Biochemistry, Institute for Cancer Research, Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway.
Antoni Wiedlocha
Anna Szlachcic
Daniel Krowarsch
Jacek Otlewski
Sjur Olsnes
Institute for Biomedicine · ITUniversity of Oslo · NOUniversity of Wrocław · PL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Human FGF1 (fibroblast growth factor 1) is a powerful signaling molecule with a short half-life in vivo and a denaturation temperature close to physiological. Binding to heparin increases the stability of FGF1 and is believed to be important in the formation of FGF1.fibroblast growth factor receptor (FGFR) active complex. In order to reveal the function of heparin in FGF1.FGFR complex formation and signaling, we constructed several FGF1 variants with reduced affinity for heparin and with diverse stability. We determined their biophysical properties and biological activities as well as their ability to translocate across cellular membranes. Our study showed that increased thermodynamic stability of FGF1 nicely compensates for decreased binding of heparin in FGFR activation, induction of DNA synthesis, and cell proliferation. By stepwise introduction of stabilizing mutations into the K118E (K132E) FGF1 variant that shows reduced affinity for heparin and is inactive in stimulation of DNA synthesis, we were able to restore the full mitogenic activity of this mutant. Our results indicate that the main role of heparin in FGF-induced signaling is to protect this naturally unstable protein against heat and/or proteolytic degradation and that heparin is not essential for a direct FGF1-FGFR interaction and receptor activation.

Indexed as

AnimalsBinding SitesCell ProliferationFibroblast Growth Factor 1HeparinHumansMiceMutagenesis, Site-DirectedNIH 3T3 CellsProtein BindingProtein ConformationProtein StabilityReceptors, Fibroblast Growth FactorSignal TransductionThermodynamicsFibroblast Growth Factor 1HeparinReceptors, Fibroblast Growth Factor

Identifiers

PMID19574212
PMCPMC2757240
OpenAlexW2101792144

What OpenQuestion holds

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LicenceCC BY-NC
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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.