Evidence map›Paper›PMID 22967899›Full record

ArticleFEBS letters2012

TPCK inhibits AGC kinases by direct activation loop adduction at phenylalanine-directed cysteine residues.

Rana Anjum, Eunice Pae, John Blenis, Bryan A Ballif

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

Article in FEBS letters, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.3field-weighted citation impact, top 42% 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

1 citing paper in PubMed, 4 citations in OpenAlex.

  1. 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

4 authors at 2 institutions in 1 country.

Rana AnjumDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Eunice Pae
John Blenis
Bryan A Ballif
Harvard University · USUniversity of Vermont · US

Funding

Vermont INBRE Administrative Supplement 2024 AWD 118P20GM103449 · NIGMS · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI Ying Wai Lam · 2012 to 2026
$58.4M
VOLATILE SIGNALING IN PHARBITIS NILP20RR016462 · NCRR · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · PI KIRSHENBAUM, ARI PHILLIP · 2001 to 2011
$31.1M
SIGNAL TRANSDUCTION TO PP70 S6KR01GM051405 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI BLENIS, JOHN · 1995 to 2023
$14.0M
ONCOGENIC REGULATION OF S6 PROTEIN KINASE &CELL GROWTHR01CA046595 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI JOHN BLENIS · 1988 to 2026
$10.6M
Mitogenic and Oncogenic Regulation of ERK/RSK SignalingR37CA046595 · NCI · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI BLENIS, JOHN · 2003 to 2012
$6.4M
TECHNOLOGY FOR AUTOMATED ANALYSIS OF PROTEOMESK22HG000041 · NHGRI · UNIVERSITY OF WASHINGTON · PI GYGI, STEVEN P · 2000 to 2004
$1.2M
INSTITUTIONAL TRAINING GRANT IN GENOMIC SCIENCET32HG000041 · NHGRI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI SMITH, TEMPLE F · 1995 to 1999
–
NCI NIH HHS CA46595NCI NIH HHS R01 CA046595NCI NIH HHS R37 CA046595NCRR NIH HHS P20 RR016462NCRR NIH HHS P20RR16462NHGRI NIH HHS HG00041NHGRI NIH HHS K22 HG000041NHGRI NIH HHS T32 HG000041NIGMS NIH HHS GM51405NIGMS NIH HHS P20 GM103449NIGMS NIH HHS R01 GM051405
6 · The paper itself

Abstract

N-alpha-tosyl-L-phenylalanyl chloromethyl ketone (TPCK) has anti-tumorigenic properties, but its direct cellular targets are unknown. Previously, we showed TPCK inhibited the PDKl-dependent AGC kinases RSK, Akt and S6K1 without inhibiting PKA, ERK1/2, PI3K, and PDK1 itself. Here we show TPCK-inhibition of the RSK-related kinases MSK1 and 2, which can be activated independently of PDK1. Mass spectrometry analysis of RSK1, Aktl, S6K1 and MSK1 immunopurified from TPCK-treated cells identified TPCK adducts on cysteines located in conserved activation loop Phenylalanine-Cysteine (Phe-Cys) motifs. Mutational analysis of the Phe-Cys residues conferred partial TPCK resistance. These studies elucidate a primary mechanism by which TPCK inhibits several AGC kinases, inviting consideration of TPCK-like compounds in chemotherapy given their potential for broad control of cellular growth, proliferation and survival.

Indexed as

Amino Acid MotifsAmino Acid SequenceAmino Acid SubstitutionBase SequenceConserved SequenceCysteineDNA PrimersHEK293 CellsHumansMolecular Sequence DataMutagenesis, Site-DirectedPhenylalanineProtein Kinase InhibitorsProtein KinasesProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktAKT1 protein, humanCysteineDNA Primersmitogen and stress-activated protein kinase 1PDK1 protein, humanPhenylalanineProtein Kinase InhibitorsProtein KinasesProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktPyruvate Dehydrogenase Acetyl-Transferring KinaseRibosomal Protein S6 Kinases, 90-kDaRPS6KA1 protein, humanRPS6KA4 protein, humanTosylphenylalanyl Chloromethyl Ketone

Identifiers

PMID22967899
PMCPMC3606710
OpenAlexW2057788239

What OpenQuestion holds

Textmetadata
LicenceTDM
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.