Evidence map›Paper›PMID 10970807›Full record

ArticleThe Biochemical journal2000

Diffusion control of protein phosphorylation in signal transduction pathways.

B N Kholodenko, G C Brown, J B Hoek

Open access · greenAbstract read
In one paragraph

Article in The Biochemical journal, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
0.7field-weighted citation impact, top 30% 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

36 citing papers in PubMed, 76 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Spatial aspects in the SMAD signaling pathway.Journal of mathematical biology · 2013
    Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Formation of morphogen gradients: local accumulation time.Physical review. E, Statistical, nonlinear, and soft matter physics · 2011
    Article
  12. Article
  13. Article
  14. Article
  15. A Cut Cell Method for Simulating Spatial Models of Biochemical Reaction Networks in Arbitrary Geometries.Communications in applied mathematics and computational science · 2010
    Article
  16. Review
  17. SIMULATING BIOCHEMICAL SIGNALING NETWORKS IN COMPLEX MOVING GEOMETRIES.SIAM journal on scientific computing : a publication of the Society for Industrial and Applied Mathematics · 2010
    Article
  18. Effects of chronic overload on muscle hypertrophy and mTOR signaling in young adult and aged rats.The journals of gerontology. Series A, Biological sciences and medical sciences · 2009
    Article
  19. Article
  20. Article
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

3 authors at 1 institution in 1 country.

B N KholodenkoDepartment of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, 1020 Locust St, Philadelphia, PA 19107, USA. Boris.Kholodenko@mail.tju.edu
G C Brown
J B Hoek
University of Cambridge · GB

Funding

Receptor Tyrosine Kinase Signaling NetworksR01GM059570 · NIGMS · THOMAS JEFFERSON UNIVERSITY · PI HOEK, JOANNES B · 2000 to 2010
$3.6M
NIAAA NIH HHS AA01786NIAAA NIH HHS AA07215NIGMS NIH HHS GM59570
6 · The paper itself

Abstract

Multiple signalling proteins are phosphorylated and dephosphorylated at separate cellular locations, which potentially causes spatial gradients of phospho-proteins within the cell. We have derived relationships that enable us to estimate the extent to which a protein kinase, a phosphatase and the diffusion of signalling proteins control the protein phosphorylation flux and the phospho-protein gradient. Two different cellular geometries were analysed: (1) the kinase is located on one planar membrane and the phosphatase on a second parallel planar membrane, and (2) the kinase is located on the plasma membrane of a spherical cell and the phosphatase is distributed homogeneously in the cytoplasm. We demonstrate that the control contribution of protein diffusion is potentially significant, given the measured rates for protein kinases, phosphatases and diffusion. If the distance between the membranes is 1 microm or greater, the control by diffusion can reach 33% or more, with the rest of the control (67%) shared by the kinase and the phosphatase. At distances of less than 0.1 microm, diffusion does not limit protein phosphorylation. For a spherical cell of radius 10 microm, a protein diffusion coefficient of 10(-8) cm(2). s(-1) and rate constants for the kinase and the phosphatase of approx. 1 s(-1), control over the phosphorylation flux resides mainly with the phosphatase and protein diffusion, with approximately equal contributions of each of these. The ratio of phospho-protein concentrations at the cell membrane and the cell centre (the dynamic compartmentation of the phospho-protein) is shown to be controlled by the rates of the protein phosphatase and of diffusion. The kinase can contribute significantly to the control of the absolute value of the phospho-protein gradient.

Indexed as

Signal TransductionCell MembraneCytosolPhosphoprotein PhosphatasesPhosphoproteinsPhosphorylationProtein KinasesPhosphoprotein PhosphatasesPhosphoproteinsProtein Kinases

Identifiers

PMID10970807
PMCPMC1221325
OpenAlexW2057554308

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.