Evidence map›Paper›PMID 16847350›Full record

ArticleGenes & development2006

Function of the MAPK scaffold protein, Ste5, requires a cryptic PH domain.

Lindsay S Garrenton, Susan L Young, Jeremy Thorner

Abstract read
In one paragraph

Article in Genes & development, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
–field-weighted citation impact
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

35 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Yeast mating: Ceramide acyl chain length matters?Cell cycle (Georgetown, Tex.) · 2018
    Article
  5. Structural basis of autoregulatory scaffolding by apoptosis signal-regulating kinase 1.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Fungal mating pheromones: choreographing the dating game.Fungal genetics and biology : FG & B · 2011
    Review
  19. Review
  20. Distribution and functions of sterols and sphingolipids.Cold Spring Harbor perspectives in biology · 2011
    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

3 authors.

Lindsay S GarrentonDepartment of Molecular and Cell Biology, Division of Biochemistry and Molecular Biology, University of California, Berkeley, 94720, USA.
Susan L Young
Jeremy Thorner

Funding

THE MOLECULAR BASIS OF CELL FUNCTIONT32GM007232 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI BILDER, DAVID, UNAL, ELCIN · 1985 to 2022
$36.4M
Yeast Protein Kinase Signaling Networks: Specificity, Regulation and FunctionR01GM021841 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI THORNER, JEREMY W. · 1985 to 2019
$11.8M
TRAINING PROGRAM IN NEUROSCIENCET32GM007048 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI FELDMAN, DANIEL · 1985 to 2015
$6.1M
REGULATORY BIOLOGY OF CANCER AND GROWTH CONTROLT32CA009041 · NCI · UNIVERSITY OF CALIFORNIA BERKELEY · PI FIRESTONE, GARY L · 1985 to 2011
$3.7M
YEAST PEPTIDE HORMONE SYNTHESIS AND SIGNAL TRANSDUCTIONR37GM021841 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI THORNER, JEREMY W. · 1989 to 1998
–
NCI NIH HHS CA09041NCI NIH HHS T32 CA009041NIGMS NIH HHS GM07048NIGMS NIH HHS GM07232NIGMS NIH HHS GM21841NIGMS NIH HHS R01 GM021841NIGMS NIH HHS T32 GM007048NIGMS NIH HHS T32 GM007232
6 · The paper itself

Abstract

Ste5, the prototypic mitogen-activated protein kinase (MAPK) scaffold protein, associates with plasma membrane-tethered Gbetagamma freed upon pheromone receptor occupancy, thereby initiating downstream signaling. We demonstrate that this interaction and membrane binding of an N-terminal amphipathic alpha-helix (PM motif) are not sufficient for Ste5 action. Rather, Ste5 contains a pleckstrin-homology (PH) domain (residues 388-518) that is essential for its membrane recruitment and function. Altering residues (R407S K411S) equivalent to those that mediate phosphoinositide binding in other PH domains abolishes Ste5 function. The isolated PH domain, but not a R407S K411S derivative, binds phosphoinositides in vitro. Ste5(R407S K411S) is expressed normally, retains Gbetagamma and Ste11 binding, and oligomerizes, yet is not recruited to the membrane in response to pheromone. Artificial membrane tethering of Ste5(R407S K411S) restores signaling. R407S K411S loss-of-function mutations abrogate the constitutive activity of gain-of-function Ste5 alleles, including one (P44L) that increases membrane affinity of the PM motif. Thus, the PH domain is essential for stable membrane recruitment of Ste5, and this association is critical for initiation of downstream signaling because it allows Ste5-bound Ste11 (MAPKKK) to be activated by membrane-bound Ste20 (MAPKKKK).

Indexed as

Adaptor Proteins, Signal TransducingAmino Acid SequenceBlood ProteinsCell MembraneGTP-Binding Protein beta SubunitsGTP-Binding Protein gamma SubunitsIntracellular Signaling Peptides and ProteinsMAP Kinase Kinase KinasesMitogen-Activated Protein KinasesMolecular Sequence DataMutationPheromonesPhosphatidylinositolsPhosphoproteinsProtein Serine-Threonine KinasesProtein Structure, TertiaryAdaptor Proteins, Signal TransducingBlood ProteinsG-protein Beta gammaGTP-Binding Protein beta SubunitsGTP-Binding Protein gamma SubunitsIntracellular Signaling Peptides and ProteinsMAP Kinase Kinase KinasesMitogen-Activated Protein KinasesPheromonesPhosphatidylinositolsPhosphoproteinsplatelet protein P47Protein Serine-Threonine KinasesSaccharomyces cerevisiae ProteinsSte11 protein, S cerevisiaeSTE20 protein, S cerevisiaeSTE5 protein, S cerevisiae

Identifiers

PMID16847350
PMCPMC1522084

What OpenQuestion holds

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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.