Evidence map›Paper›PMID 28314095›Full record

ArticleACS chemical biology2017

Rational Redesign of a Functional Protein Kinase-Substrate Interaction.

Catherine Chen, Wutigri Nimlamool, Chad J Miller, Hua Jane Lou, Benjamin E Turk

Abstract read
In one paragraph

Article in ACS chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.5field-weighted citation impact, top 19% 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

12 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. The Leaf Extract ofBioMed research international · 2022
    Article
  7. Article
  8. Essential Oil fromPlants (Basel, Switzerland) · 2021
    Article
  9. Article
  10. Article
  11. Review
  12. 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

5 authors at 1 institution in 2 countries.

Catherine ChenDepartment of Pharmacology, Yale University School of Medicine , New Haven, Connecticut 06520, United States.
Wutigri NimlamoolDepartment of Pharmacology, Yale University School of Medicine , New Haven, Connecticut 06520, United States.
Chad J MillerDepartment of Pharmacology, Yale University School of Medicine , New Haven, Connecticut 06520, United States.
Hua Jane LouDepartment of Pharmacology, Yale University School of Medicine , New Haven, Connecticut 06520, United States.
Benjamin E TurkDepartment of Pharmacology, Yale University School of Medicine , New Haven, Connecticut 06520, United States.ORCID 0000-0001-9275-4069
Yale University · US

Funding

INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDT32GM007324 · NIGMS · YALE UNIVERSITY · PI BENNETT, ANTON M · 1987 to 2022
$6.2M
Structure-directed investigations into the regulation of Ste20 kinasesR01GM102262 · NIGMS · YALE UNIVERSITY · PI BOGGON, TITUS JONATHON · 2012 to 2025
$4.2M
BIOCHEMICAL ASPECTS OF CHEMOTHERAPYT32CA009085 · NCI · YALE UNIVERSITY · PI CHENG, YUNG-CHI · 1985 to 2009
$2.8M
Modeling human phosphorylation networks through kinome-wide profilingR01GM104047 · NIGMS · YALE UNIVERSITY · PI TURK, BENJAMIN E, YAFFE, MICHAEL B · 2013 to 2017
$2.4M
NCI NIH HHS T32 CA009085NIGMS NIH HHS R01 GM102262NIGMS NIH HHS R01 GM104047NIGMS NIH HHS T32 GM007324
6 · The paper itself

Abstract

Eukaryotic protein kinases typically phosphorylate substrates in the context of specific sequence motifs, contributing to specificity essential for accurate signal transmission. Protein kinases recognize their target sequences through complementary interactions within the active site cleft. As a step toward the construction of orthogonal kinase signaling systems, we have re-engineered the protein kinase Pim1 to alter its phosphorylation consensus sequence. Residues in the Pim1 catalytic domain interacting directly with a critical arginine residue in the substrate were substituted to produce a kinase mutant that instead accommodates a hydrophobic residue. We then introduced a compensating mutation into a Pim1 substrate, the pro-apoptotic protein BAD, to reconstitute phosphorylation both in vitro and in living cells. Coexpression of the redesigned kinase with its substrate in cells protected them from apoptosis. Such orthogonal kinase-substrate pairs provide tools to probe the functional consequences of specific phosphorylation events in living cells and to design synthetic signaling pathways.

Indexed as

Apoptosisbcl-Associated Death ProteinCatalytic DomainHEK293 CellsHumansMutation, MissenseProtein EngineeringProtein KinasesProto-Oncogene Proteins c-pim-1Substrate Specificitybcl-Associated Death ProteinProtein KinasesProto-Oncogene Proteins c-pim-1

Identifiers

PMID28314095
PMCPMC5442603
OpenAlexW2595058357

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.