Evidence map›Paper›PMID 27075707›Full record

ArticleMolecular endocrinology (Baltimore, Md.)2016

TIMP3 Modulates GHR Abundance and GH Sensitivity.

Yue Zhang, Xiangdong Wang, Kimberly Loesch, Larry A May, George E Davis, Jing Jiang, Stuart J Frank

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

Article in Molecular endocrinology (Baltimore, Md.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

7 citing papers in PubMed, 14 citations in OpenAlex.

  1. Growth Hormone, Not Simply Just a Hormone for Growth.Endocrinology and metabolism (Seoul, Korea) · 2026
    Review
  2. Review
  3. Article
  4. Review
  5. Classical and novel GH receptor signaling pathways.Molecular and cellular endocrinology · 2020
    Review
  6. Article
  7. Growth Hormone Resistance-Special Focus on Inflammatory Bowel Disease.International journal of molecular sciences · 2017
    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

7 authors at 5 institutions in 2 countries.

Yue ZhangDepartment of Medicine (Y.Z., J.J., S.J.F.), Division of Endocrinology, Diabetes, and Metabolism, and Department of Cell, Developmental, and Integrative Biology (S.J.F.), University of Alabama at Birmingham, Birmingham, Alabama 35294; The Institute of Cell Biology (X.W.), Shandong University School of Medicine, Jinan 250012, China; Department of Biochemistry and Biophysics (K.L.), Texas A&M University, College Station, Texas 77843; Department of Surgery (L.A.M.), University of Tennessee College of Medicine Chattanooga, Chattanooga, Tennessee 37403; Department of Medical Pharmacology and Physiology (G.E.D.), University of Missouri School of Medicine, Columbia, Missouri 65212; and Endocrinology Section (S.J.F.), Medical Service, Veterans Affairs Medical Center, Birmingham, Alabama 35233.
Xiangdong WangDepartment of Medicine (Y.Z., J.J., S.J.F.), Division of Endocrinology, Diabetes, and Metabolism, and Department of Cell, Developmental, and Integrative Biology (S.J.F.), University of Alabama at Birmingham, Birmingham, Alabama 35294; The Institute of Cell Biology (X.W.), Shandong University School of Medicine, Jinan 250012, China; Department of Biochemistry and Biophysics (K.L.), Texas A&M University, College Station, Texas 77843; Department of Surgery (L.A.M.), University of Tennessee College of Medicine Chattanooga, Chattanooga, Tennessee 37403; Department of Medical Pharmacology and Physiology (G.E.D.), University of Missouri School of Medicine, Columbia, Missouri 65212; and Endocrinology Section (S.J.F.), Medical Service, Veterans Affairs Medical Center, Birmingham, Alabama 35233.
Kimberly LoeschDepartment of Medicine (Y.Z., J.J., S.J.F.), Division of Endocrinology, Diabetes, and Metabolism, and Department of Cell, Developmental, and Integrative Biology (S.J.F.), University of Alabama at Birmingham, Birmingham, Alabama 35294; The Institute of Cell Biology (X.W.), Shandong University School of Medicine, Jinan 250012, China; Department of Biochemistry and Biophysics (K.L.), Texas A&M University, College Station, Texas 77843; Department of Surgery (L.A.M.), University of Tennessee College of Medicine Chattanooga, Chattanooga, Tennessee 37403; Department of Medical Pharmacology and Physiology (G.E.D.), University of Missouri School of Medicine, Columbia, Missouri 65212; and Endocrinology Section (S.J.F.), Medical Service, Veterans Affairs Medical Center, Birmingham, Alabama 35233.
Larry A MayDepartment of Medicine (Y.Z., J.J., S.J.F.), Division of Endocrinology, Diabetes, and Metabolism, and Department of Cell, Developmental, and Integrative Biology (S.J.F.), University of Alabama at Birmingham, Birmingham, Alabama 35294; The Institute of Cell Biology (X.W.), Shandong University School of Medicine, Jinan 250012, China; Department of Biochemistry and Biophysics (K.L.), Texas A&M University, College Station, Texas 77843; Department of Surgery (L.A.M.), University of Tennessee College of Medicine Chattanooga, Chattanooga, Tennessee 37403; Department of Medical Pharmacology and Physiology (G.E.D.), University of Missouri School of Medicine, Columbia, Missouri 65212; and Endocrinology Section (S.J.F.), Medical Service, Veterans Affairs Medical Center, Birmingham, Alabama 35233.
George E DavisDepartment of Medicine (Y.Z., J.J., S.J.F.), Division of Endocrinology, Diabetes, and Metabolism, and Department of Cell, Developmental, and Integrative Biology (S.J.F.), University of Alabama at Birmingham, Birmingham, Alabama 35294; The Institute of Cell Biology (X.W.), Shandong University School of Medicine, Jinan 250012, China; Department of Biochemistry and Biophysics (K.L.), Texas A&M University, College Station, Texas 77843; Department of Surgery (L.A.M.), University of Tennessee College of Medicine Chattanooga, Chattanooga, Tennessee 37403; Department of Medical Pharmacology and Physiology (G.E.D.), University of Missouri School of Medicine, Columbia, Missouri 65212; and Endocrinology Section (S.J.F.), Medical Service, Veterans Affairs Medical Center, Birmingham, Alabama 35233.
Jing JiangDepartment of Medicine (Y.Z., J.J., S.J.F.), Division of Endocrinology, Diabetes, and Metabolism, and Department of Cell, Developmental, and Integrative Biology (S.J.F.), University of Alabama at Birmingham, Birmingham, Alabama 35294; The Institute of Cell Biology (X.W.), Shandong University School of Medicine, Jinan 250012, China; Department of Biochemistry and Biophysics (K.L.), Texas A&M University, College Station, Texas 77843; Department of Surgery (L.A.M.), University of Tennessee College of Medicine Chattanooga, Chattanooga, Tennessee 37403; Department of Medical Pharmacology and Physiology (G.E.D.), University of Missouri School of Medicine, Columbia, Missouri 65212; and Endocrinology Section (S.J.F.), Medical Service, Veterans Affairs Medical Center, Birmingham, Alabama 35233.
Stuart J FrankDepartment of Medicine (Y.Z., J.J., S.J.F.), Division of Endocrinology, Diabetes, and Metabolism, and Department of Cell, Developmental, and Integrative Biology (S.J.F.), University of Alabama at Birmingham, Birmingham, Alabama 35294; The Institute of Cell Biology (X.W.), Shandong University School of Medicine, Jinan 250012, China; Department of Biochemistry and Biophysics (K.L.), Texas A&M University, College Station, Texas 77843; Department of Surgery (L.A.M.), University of Tennessee College of Medicine Chattanooga, Chattanooga, Tennessee 37403; Department of Medical Pharmacology and Physiology (G.E.D.), University of Missouri School of Medicine, Columbia, Missouri 65212; and Endocrinology Section (S.J.F.), Medical Service, Veterans Affairs Medical Center, Birmingham, Alabama 35233.
University of Alabama at Birmingham · USShandong University · CNTexas A&M University · USUniversity of Missouri · USUniversity of Tennessee at Chattanooga · US

Funding

Tyrosine Phosphorylation and Growth Hormone SignallingR01DK046395 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI FRANK, STUART J · 1997 to 2013
$3.5M
Growth Hormone Receptor Dimerization/Disulfide LinkageR01DK058259 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI FRANK, STUART J · 2001 to 2014
$3.4M
Growth Hormone Receptor Dimerization/Disulfide LinkageR56DK058259 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI FRANK, STUART J · 2010 to 2010
$220k
Tyrosine Phosphyorylation and Growth Hormone SignalingR56DK046395 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI FRANK, STUART J. · 2005 to 2005
$27k
NIDDK NIH HHS R01 DK046395NIDDK NIH HHS R01 DK058259NIDDK NIH HHS R56 DK046395NIDDK NIH HHS R56 DK058259
6 · The paper itself

Abstract

GH receptor (GHR) binds GH at the cell surface via its extracellular domain and initiates intracellular signal transduction, resulting in important anabolic and metabolic actions. GH signaling is subject to dynamic regulation, which in part is exerted by modulation of cell surface GHR levels. Constitutive and inducible metalloprotease-mediated cleavage of GHR regulate GHR abundance and thereby modulate GH action. We previously demonstrated that GHR proteolysis is catalyzed by the TNF-α converting enzyme (TACE; ADAM17). Tissue inhibitors of metalloproteases-3 (TIMP3) is a natural specific inhibitor of TACE, although mechanisms underlying this inhibition are not yet fully understood. In the current study, we use two model cell lines to examine the relationships between cellular TACE, TIMP3 expression, GHR metalloproteolysis, and GH sensitivity. These two cell lines exhibited markedly different sensitivity to inducible GHR proteolysis, which correlated directly to their relative levels of mature TACE vs unprocessed TACE precursor and indirectly to their levels of cellular TIMP3. Our results implicate TIMP3 as a modulator of cell surface GHR abundance and the ability of GH to promote cellular signaling; these modulatory effects may be conferred by endogenous TIMP3 expression as well as exogenous TIMP3 exposure. Furthermore, our analysis suggests that TIMP3, in addition to regulating the activity of TACE, may also modulate the maturation of TACE, thereby affecting the abundance of the active form of the enzyme.

Indexed as

ADAM17 ProteinAnimalsGene SilencingGrowth HormoneHEK293 CellsHumansJanus Kinase 2MiceModels, BiologicalProteolysisReceptors, SomatotropinSTAT5 Transcription FactorTetradecanoylphorbol AcetateTissue Inhibitor of Metalloproteinase-3ADAM17 ProteinGrowth HormoneJanus Kinase 2Receptors, SomatotropinSTAT5 Transcription FactorTetradecanoylphorbol AcetateTissue Inhibitor of Metalloproteinase-3

Identifiers

PMID27075707
PMCPMC4884343
OpenAlexW2413016093

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.