Evidence map›Paper›PMID 20584982›Full record

ArticleMolecular and cellular biology2010

Myristoylation and membrane binding regulate c-Src stability and kinase activity.

Parag Patwardhan, Marilyn D Resh

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.

0numbers the graph read from it
0cells of the map it votes in
107citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

107 citing papers in PubMed, 176 citations in OpenAlex.

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  15. Emerging Roles of YES1 in Cancer: The Putative Target in Drug Resistance.International journal of molecular sciences · 2024
    Review
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47 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

2 authors at 1 institution in 1 country.

Parag PatwardhanCell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Marilyn D Resh
Memorial Sloan Kettering Cancer Center · US

Funding

Palmitoylation of Hedgehog ProteinsR01GM057966 · NIGMS · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI RESH, MARILYN D · 1998 to 2011
$3.2M
NIGMS NIH HHS GM57966NIGMS NIH HHS R01 GM057966
6 · The paper itself

Abstract

Myristoylation is critical for membrane association of Src kinases, but a role for myristate in regulating other aspects of Src biology has not been explored. In the c-Abl tyrosine kinase, myristate binds within a hydrophobic pocket at the base of the kinase domain and latches the protein into an autoinhibitory conformation. A similar pocket has been predicted to exist in c-Src, raising the possibility that Src might also be regulated by myristoylation. Here we show that in contrast to the case for c-Abl, myristoylation exerts a positive effect on c-Src kinase activity. We also demonstrate that myristoylation and membrane binding regulate c-Src ubiquitination and degradation. Nonmyristoylated c-Src exhibited reduced kinase activity but had enhanced stability compared to myristoylated c-Src. We then mutated critical residues in the predicted myristate binding pocket of c-Src. Mutation of L360 and/or E486 had no effect on c-Src membrane binding or localization. However, constructs containing a T456A mutation were partially released from the membrane, suggesting that mutagenesis could induce c-Src to undergo an artificial myristoyl switch. All of the pocket mutants exhibited decreased kinase activity. We concluded that myristoylation and the pocket residues regulate c-Src, but in a manner very different from that for c-Abl.

Indexed as

AnimalsBinding SitesCell MembraneChickensChlorocebus aethiopsCOS CellsGene Expression RegulationMyristic AcidProtein BindingProtein StabilityProto-Oncogene Proteins c-cblsrc-Family KinasesUbiquitinationMyristic AcidProto-Oncogene Proteins c-cblsrc-Family Kinases

Identifiers

PMID20584982
PMCPMC2937550
OpenAlexW1982853447

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.