Evidence map›Paper›PMID 25999467›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015

Tyrosine phosphorylation of RAS by ABL allosterically enhances effector binding.

Pamela Y Ting, Christian W Johnson, Cong Fang, Xiaoqing Cao, Thomas G Graeber, Carla Mattos, John Colicelli

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

29 citing papers in PubMed, 46 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Allosteric site variants affect GTP hydrolysis on Ras.Protein science : a publication of the Protein Society · 2023
    Article
  7. Regulation of Ras Signaling by S-Nitrosylation.Antioxidants (Basel, Switzerland) · 2023
    Review
  8. Article
  9. Dynamic regulation of RAS and RAS signaling.The Biochemical journal · 2023
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Therapeutic targeting of RAS: New hope for drugging the "undruggable".Biochimica et biophysica acta. Molecular cell research · 2020
    Review
  20. Review
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

7 authors at 1 institution in 1 country.

Pamela Y Ting*Molecular Biology Institute, Jonsson Comprehensive Cancer Center, Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA; Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts, USA; and Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, University of California at Los Angeles Metabolomics and Proteomics Center, California Nanosystems Institute and Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California, USA.
Christian W Johnson*Molecular Biology Institute, Jonsson Comprehensive Cancer Center, Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA; Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts, USA; and Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, University of California at Los Angeles Metabolomics and Proteomics Center, California Nanosystems Institute and Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California, USA.
Cong Fang*Molecular Biology Institute, Jonsson Comprehensive Cancer Center, Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA; Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts, USA; and Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, University of California at Los Angeles Metabolomics and Proteomics Center, California Nanosystems Institute and Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California, USA.
Xiaoqing Cao*Molecular Biology Institute, Jonsson Comprehensive Cancer Center, Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA; Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts, USA; and Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, University of California at Los Angeles Metabolomics and Proteomics Center, California Nanosystems Institute and Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California, USA.
Thomas G Graeber*Molecular Biology Institute, Jonsson Comprehensive Cancer Center, Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA; Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts, USA; and Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, University of California at Los Angeles Metabolomics and Proteomics Center, California Nanosystems Institute and Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California, USA.
Carla Mattos*Molecular Biology Institute, Jonsson Comprehensive Cancer Center, Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA; Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts, USA; and Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, University of California at Los Angeles Metabolomics and Proteomics Center, California Nanosystems Institute and Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California, USA.
John Colicelli*Molecular Biology Institute, Jonsson Comprehensive Cancer Center, Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA; Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts, USA; and Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, University of California at Los Angeles Metabolomics and Proteomics Center, California Nanosystems Institute and Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California, USA colicelli@mednet.ucla.edu.
University of California, Los Angeles · US

Funding

UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
UCLA NIGMS T32 Program AssessmentT32GM007185 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TORRES, JORGE · 1985 to 2020
$21.7M
TARGETED COMBINATORIAL TREATMENT OF BRAF MELANOMASP01CA168585 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DRY, SARAH M. · 2013 to 2017
$8.4M
A Novel Screen for Compounds that Outflank BCR-ABL Drug-ResistanceR01CA136699 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI COLICELLI, JOHN J. · 2009 to 2011
$937k
NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1TR000124NCI NIH HHS CA136699NCI NIH HHS CA168585NCI NIH HHS P01 CA168585NCI NIH HHS R01 CA136699NIGMS NIH HHS GM007185NIGMS NIH HHS T32 GM007185
6 · The paper itself

Abstract

RAS proteins are signal transduction gatekeepers that mediate cell growth, survival, and differentiation through interactions with multiple effector proteins. The RAS effector RAS- and RAB-interacting protein 1 (RIN1) activates its own downstream effectors, the small GTPase RAB5 and the tyrosine kinase Abelson tyrosine-protein kinase (ABL), to modulate endocytosis and cytoskeleton remodeling. To identify ABL substrates downstream of RAS-to-RIN1 signaling, we examined human HEK293T cells overexpressing components of this pathway. Proteomic analysis revealed several novel phosphotyrosine peptides, including Harvey rat sarcoma oncogene (HRAS)-pTyr(137). Here we report that ABL phosphorylates tyrosine 137 of H-, K-, and NRAS. Increased RIN1 levels enhanced HRAS-Tyr(137) phosphorylation by nearly 5-fold, suggesting that RAS-stimulated RIN1 can drive ABL-mediated RAS modification in a feedback circuit. Tyr(137) is well conserved among RAS orthologs and is part of a transprotein H-bond network. Crystal structures of HRAS(Y137F) and HRAS(Y137E) revealed conformation changes radiating from the mutated residue. Although consistent with Tyr(137) participation in allosteric control of HRAS function, the mutations did not alter intrinsic GTP hydrolysis rates in vitro. HRAS-Tyr(137) phosphorylation enhanced HRAS signaling capacity in cells, however, as reflected by a 4-fold increase in the association of phosphorylated HRAS(G12V) with its effector protein RAF proto-oncogene serine/threonine protein kinase 1 (RAF1). These data suggest that RAS phosphorylation at Tyr(137) allosterically alters protein conformation and effector binding, providing a mechanism for effector-initiated modulation of RAS signaling.

Indexed as

Amino Acid SubstitutionAnimalsHEK293 CellsHumansIntracellular Signaling Peptides and ProteinsMutation, MissenseOncogene Proteins v-ablPhosphorylationProto-Oncogene MasProto-Oncogene Proteins p21(ras)rab5 GTP-Binding Proteinsraf KinasesRatsSignal TransductionTyrosineIntracellular Signaling Peptides and ProteinsMAS1 protein, humanOncogene Proteins v-ablProto-Oncogene MasProto-Oncogene Proteins p21(ras)RAB5C protein, humanrab5 GTP-Binding Proteinsraf KinasesRIN1 protein, humanTyrosineGTPaseRAF1RIN1signal transduction

Identifiers

PMID25999467
PMCPMC4550377
OpenAlexW2135875529

What Socratic 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 Socratic graph.