Evidence map›Paper›PMID 28955922›Full record

ArticleBiochemistry and biophysics reports2016

Direct coupling of the HER4 intracellular domain (4ICD) and STAT5A signaling is required to induce mammary epithelial cell differentiation.

Wen Han, Mary E Sfondouris, Frank E Jones

Open access · goldAbstract read
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In one paragraph

Article in Biochemistry and biophysics reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.3field-weighted citation impact, top 34% 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

4 citing papers in PubMed, 8 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

3 authors at 1 institution in 1 country.

Wen HanDepartment of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA.
Mary E SfondourisDepartment of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA.
Frank E JonesDepartment of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA.
Tulane University · US

Funding

ERBB4 signaling in the normal and neoplastic breastR01CA095783 · NCI · UNIVERSITY OF COLORADO DENVER · PI JONES, FRANK E · 2001 to 2013
$3.4M
Influence of ErbB4 activity on metastatic breast cancerR01CA096717 · NCI · UNIVERSITY OF COLORADO DENVER · PI JONES, FRANK E · 2003 to 2007
$1.8M
NCI NIH HHS R01 CA095783NCI NIH HHS R01 CA096717
6 · The paper itself

Abstract

The HER4 receptor tyrosine kinase and STAT5A cooperate to promote mammary luminal progenitor cell maturation and mammary epithelial cell differentiation. Coupled HER4 and STAT5A signaling is mediated, in part, through association of the HER4 intracellular domain (4ICD) with STAT5A at STAT5A target gene promoters where 4ICD functions as a STAT5A transcriptional coactivator. Despite an essential role for coupled 4ICD and STAT5A signaling in mammary gland development, the mechanistic basis of 4ICD and STAT5A cooperative signaling remains unexplored. Here we show for the first time that 4ICD and STAT5A directly interact through STAT5A recruitment and binding to HER4/4ICD residue Y984. Accordingly, altering the 4ICD Y984 to phenylalanine results in a dramatic reduction of STAT5A and 4ICD-Y984F interacting complexes coimmunoprecipitated with HER4 or STAT5A specific antibodies. We further show that disrupting the 4ICD and STAT5A interaction has an important physiological impact on mammary epithelial cell differentiation. HC11 mammary epithelial cells with stable expression of 4ICD undergo differentiation with significantly increased expression of the STAT5A target genes and differentiation markers β-casein and WAP. In contrast, HC11 cells stably expressing 4ICD-Y984F failed to undergo differentiation with basal expression levels of β-casein and WAP. Differentiation in this cell system was induced in the absence of exogenous prolactin indicating that 4ICD activity is sufficient to induce mammary epithelial cell differentiation. Finally, we show that suppression of STAT5A expression abolishes the ability of 4ICD to induce HC11 differentiation and activate β-casein or WAP expression. Taken together our results demonstrate for the first time that direct coupling of 4ICD and STAT5A is both necessary and sufficient to drive mammary epithelial differentiation. In conclusion, our findings that 4ICD and STAT5A directly interact to form a physiologically important transcriptional activation complex, provide a mechanistic basis for the

Indexed as

4ICD, HER4 intracellular domainATCC, American type culture collectionEGF, epidermal growth factorEGFP, enhanced green fluorescent proteinEGFR, epidermal growth factor familyEGFR-familyERα, estrogen receptor alphaFBS, fetal bovine serumGene expressionHEK, human embryonic kidneyHER4/ERBB4HRGα1, heregulin beta 1HRGα, heregulin alphaMammary epithelial differentiationNLS, nuclear localization signalPCR, polymerase chain reactionPI3K, phosphoinositide 3-kinaseRIP, regulated intramembrane cleavageRTK, receptor tyrosine kinaseRT, reverse transcriptionSH2, src homology 2STAT5ASTAT5A, signal transducer and activator of transcription 5ATACE, tumor necrosis factor-α-converting enzymeTransactivationWAP, whey acidic proteinYAP, yes-associated protein

Identifiers

PMID28955922
PMCPMC5613636
OpenAlexW2490279214

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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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.