Evidence map›Paper›PMID 23418348›Full record

ArticleJournal of cell science2013

cGMP-dependent protein kinase Iβ regulates breast cancer cell migration and invasion via interaction with the actin/myosin-associated protein caldesmon.

Raphaela Schwappacher, Hema Rangaswami, Jacqueline Su-Yuo, Aaron Hassad, Ryan Spitler, Darren E Casteel

Open access · bronzeAbstract read
In one paragraph

Article in Journal of cell science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.6field-weighted citation impact, top 11% 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

24 citing papers in PubMed, 34 citations in OpenAlex.

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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

6 authors at 2 institutions in 1 country.

Raphaela SchwappacherDepartment of Medicine and Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.
Hema Rangaswami
Jacqueline Su-Yuo
Aaron Hassad
Ryan Spitler
Darren E Casteel
University of California, San Diego · USUniversity of California, Irvine · US

Funding

U of Calif, San Diego Neuroscience Microscopy ImagingP30NS047101 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G, ZHENG, BINHAI · 2003 to 2022
$9.0M
Study of mTOR Regulation by Rheb Using Deuterium Exchange Mass SpectrometryK22CA124517 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CASTEEL, DARREN E · 2007 to 2009
$423k
NCI NIH HHS K22 CA124517NCI NIH HHS K22-CA124517NINDS NIH HHS P30 NS047101
6 · The paper itself

Abstract

The two isoforms of type I cGMP-dependent protein kinase (PKGIα and PKGIβ) differ in their first ∼100 amino acids, giving each isoform unique dimerization and autoinhibitory domains. The dimerization domains form coiled-coil structures and serve as platforms for isoform-specific protein-protein interactions. Using the PKGIβ dimerization domain as an affinity probe in a proteomic screen, we identified the actin/myosin-associated protein caldesmon (CaD) as a PKGIβ-specific binding protein. PKGIβ phosphorylated human CaD on serine 12 in vitro and in intact cells. Phosphorylation on serine 12 or mutation of serine 12 to glutamic acid (S12E) reduced the interaction between CaD and myosin IIA. Because CaD inhibits myosin ATPase activity and regulates cell motility, we examined the effects of PKGIβ and CaD on cell migration and invasion. Inhibition of the NO/cGMP/PKG pathway reduced migration and invasion of human breast cancer cells, whereas PKG activation enhanced their motility and invasion. siRNA-mediated knockdown of endogenous CaD had pro-migratory and pro-invasive effects in human breast cancer cells. Reconstituting cells with wild-type CaD slowed migration and invasion; however, CaD containing a phospho-mimetic S12E mutation failed to reverse the pro-migratory and pro-invasive activity of CaD depletion. Our data suggest that PKGIβ enhances breast cancer cell motility and invasive capacity, at least in part, by phosphorylating CaD. These findings identify a pro-migratory and pro-invasive function for PKGIβ in human breast cancer cells, suggesting that PKGIβ is a potential target for breast cancer treatment.

Indexed as

ActinsBreast NeoplasmsCalmodulin-Binding ProteinsCell Line, TumorCell MovementCyclic GMP-Dependent Protein Kinase Type IFemaleHumansMass SpectrometryMyosinsActinsCalmodulin-Binding ProteinsCyclic GMP-Dependent Protein Kinase Type IMyosinsCaldesmoncGMP-dependent protein kinaseHuman breast cancer cellsInvasionMigration

Identifiers

PMID23418348
PMCPMC3647439
OpenAlexW2062396873

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.