Evidence map›Paper›PMID 19366211›Full record

ArticleBiochemistry2009

Regulatory autophosphorylation sites on protein kinase C-delta at threonine-141 and threonine-295.

Vitalyi O Rybin, Jianfen Guo, Erin Harleton, Steven J Feinmark, Susan F Steinberg

Open access · greenAbstract read
In one paragraph

Article in Biochemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.8field-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

11 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
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  3. Review
  4. Article
  5. Article
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  8. Article
  9. Cardiac actions of protein kinase C isoforms.Physiology (Bethesda, Md.) · 2012
    Review
  10. Article
  11. 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

5 authors at 1 institution in 1 country.

Vitalyi O RybinDepartment of Pharmacology, Columbia University, New York, New York 10032, USA.
Jianfen Guo
Erin Harleton
Steven J Feinmark
Susan F Steinberg
Columbia University · US

Funding

Protein kinase C-delta actions in cardiomyocytesR01HL077860 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI STEINBERG, SUSAN F · 2004 to 2013
$3.4M
CLINICAL AND TRANSLATIONAL SCIENCE AWARDTL1RR024158 · NCRR · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2006 to 2011
$1.6M
NCRR NIH HHS TL1 RR024158NHLBI NIH HHS HL 77860NHLBI NIH HHS R01 HL077860
6 · The paper itself

Abstract

Protein kinase C-delta (PKCdelta) is a Ser/Thr kinase that regulates a wide range of cellular responses. This study identifies novel in vitro PKCdelta autophosphorylation sites at Thr(141) adjacent to the pseudosubstrate domain, Thr(218) in the C1A-C1B interdomain, Ser(295), Ser(302), and Ser(304) in the hinge region, and Ser(503) adjacent to Thr(505) in the activation loop. Cell-based studies show that Thr(141) and Thr(295) also are phosphorylated in vivo and that Thr(141) phosphorylation regulates the kinetics of PKCdelta downregulation in COS7 cells. In vitro studies implicate Thr(141) and Thr(295) autophosphorylation as modifications that regulate PKCdelta activity. A T141D substitution markedly increases basal lipid-independent PKCdelta activity; the PKCdelta-T141D mutant is only slightly further stimulated in vitro by PMA treatment, suggesting that Thr(141) phosphorylation relieves autoinhibitory constraints that limit PKCdelta activity. Mutagenesis studies also indicate that a phosphorylation at Thr(295) contributes to the control of PKCdelta substrate specificity. We previously demonstrated that PKCdelta phosphorylates the myofilament protein cardiac troponin I (cTnI) at Ser(23)/Ser(24) when it is allosterically activated by lipid cofactors and that the Thr(505)/Tyr(311)-phosphorylated form of PKCdelta (that is present in assays with Src) acquires as additional activity toward cTnI-Thr(144). Studies reported herein show that a T505A substitution reduces PKCdelta-Thr(295) autophosphorylation and that a T295A substitution leads to a defect in Src-dependent PKCdelta-Tyr(311) phosphorylation and PKCdelta-dependent cTnI-Thr(144) phosphorylation. These results implicate PKCdelta-Thr(295) autophosphorylation as a lipid-dependent modification that links PKCdelta-Thr(505) phosphorylation to Src-dependent regulation of PKCdelta catalytic function. Collectively, these studies identify novel regulatory autophosphorylations on PKCdelta that serve as markers and regulators of PKCdelta activity.

Indexed as

ThreonineAmino Acid SequenceAmino Acid SubstitutionAnimalsBiocatalysisChlorocebus aethiopsCOS CellsDown-RegulationEnzyme ActivationHumansMiceMolecular Sequence DataPhosphorylationProtein Kinase C-deltaRatsSerineProtein Kinase C-deltaSerineThreonine

Identifiers

PMID19366211
PMCPMC2737367
OpenAlexW293008907

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.