Evidence map›Paper›PMID 27003442›Full record

ArticleMolecular endocrinology (Baltimore, Md.)2016

GHR/PRLR Heteromultimer Is Composed of GHR Homodimers and PRLR Homodimers.

Ying Liu, Yue Zhang, Jing Jiang, Peter E Lobie, Ramasamy Paulmurugan, John F Langenheim, Wen Y Chen, Kurt R Zinn, 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
1.2field-weighted citation impact, top 19% 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, 25 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Classical and novel GH receptor signaling pathways.Molecular and cellular endocrinology · 2020
    Review
  5. Review
  6. Article
  7. 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

9 authors at 3 institutions in 3 countries.

Ying LiuDepartment of Medicine (Y.L., Y.Z., J.J., S.J.F.), Division of Endocrinology, Diabetes, and Metabolism; Department of Radiology (K.R.Z.); and Department of Cell, Developmental, and Integrative Biology (S.J.F.), University of Alabama at Birmingham, Birmingham, Alabama 35294; Cancer Science Institute of Singapore and Department of Pharmacology (P.E.L.), National University of Singapore, Singapore 119077; Department of Radiology (R.P.), Stanford University School of Medicine, Palo Alto, California 94304; Department of Biological Sciences (J.F.L., W.Y.C.), Clemson University, Clemson, South Carolina 29634; and Endocrinology Section (S.J.F.), Medical Service, Veterans Affairs Medical Center, Birmingham, Alabama 35233.
Yue ZhangDepartment of Medicine (Y.L., Y.Z., J.J., S.J.F.), Division of Endocrinology, Diabetes, and Metabolism; Department of Radiology (K.R.Z.); and Department of Cell, Developmental, and Integrative Biology (S.J.F.), University of Alabama at Birmingham, Birmingham, Alabama 35294; Cancer Science Institute of Singapore and Department of Pharmacology (P.E.L.), National University of Singapore, Singapore 119077; Department of Radiology (R.P.), Stanford University School of Medicine, Palo Alto, California 94304; Department of Biological Sciences (J.F.L., W.Y.C.), Clemson University, Clemson, South Carolina 29634; and Endocrinology Section (S.J.F.), Medical Service, Veterans Affairs Medical Center, Birmingham, Alabama 35233.
Jing JiangDepartment of Medicine (Y.L., Y.Z., J.J., S.J.F.), Division of Endocrinology, Diabetes, and Metabolism; Department of Radiology (K.R.Z.); and Department of Cell, Developmental, and Integrative Biology (S.J.F.), University of Alabama at Birmingham, Birmingham, Alabama 35294; Cancer Science Institute of Singapore and Department of Pharmacology (P.E.L.), National University of Singapore, Singapore 119077; Department of Radiology (R.P.), Stanford University School of Medicine, Palo Alto, California 94304; Department of Biological Sciences (J.F.L., W.Y.C.), Clemson University, Clemson, South Carolina 29634; and Endocrinology Section (S.J.F.), Medical Service, Veterans Affairs Medical Center, Birmingham, Alabama 35233.
Peter E LobieDepartment of Medicine (Y.L., Y.Z., J.J., S.J.F.), Division of Endocrinology, Diabetes, and Metabolism; Department of Radiology (K.R.Z.); and Department of Cell, Developmental, and Integrative Biology (S.J.F.), University of Alabama at Birmingham, Birmingham, Alabama 35294; Cancer Science Institute of Singapore and Department of Pharmacology (P.E.L.), National University of Singapore, Singapore 119077; Department of Radiology (R.P.), Stanford University School of Medicine, Palo Alto, California 94304; Department of Biological Sciences (J.F.L., W.Y.C.), Clemson University, Clemson, South Carolina 29634; and Endocrinology Section (S.J.F.), Medical Service, Veterans Affairs Medical Center, Birmingham, Alabama 35233.
Ramasamy PaulmuruganDepartment of Medicine (Y.L., Y.Z., J.J., S.J.F.), Division of Endocrinology, Diabetes, and Metabolism; Department of Radiology (K.R.Z.); and Department of Cell, Developmental, and Integrative Biology (S.J.F.), University of Alabama at Birmingham, Birmingham, Alabama 35294; Cancer Science Institute of Singapore and Department of Pharmacology (P.E.L.), National University of Singapore, Singapore 119077; Department of Radiology (R.P.), Stanford University School of Medicine, Palo Alto, California 94304; Department of Biological Sciences (J.F.L., W.Y.C.), Clemson University, Clemson, South Carolina 29634; and Endocrinology Section (S.J.F.), Medical Service, Veterans Affairs Medical Center, Birmingham, Alabama 35233.
John F LangenheimDepartment of Medicine (Y.L., Y.Z., J.J., S.J.F.), Division of Endocrinology, Diabetes, and Metabolism; Department of Radiology (K.R.Z.); and Department of Cell, Developmental, and Integrative Biology (S.J.F.), University of Alabama at Birmingham, Birmingham, Alabama 35294; Cancer Science Institute of Singapore and Department of Pharmacology (P.E.L.), National University of Singapore, Singapore 119077; Department of Radiology (R.P.), Stanford University School of Medicine, Palo Alto, California 94304; Department of Biological Sciences (J.F.L., W.Y.C.), Clemson University, Clemson, South Carolina 29634; and Endocrinology Section (S.J.F.), Medical Service, Veterans Affairs Medical Center, Birmingham, Alabama 35233.
Wen Y ChenDepartment of Medicine (Y.L., Y.Z., J.J., S.J.F.), Division of Endocrinology, Diabetes, and Metabolism; Department of Radiology (K.R.Z.); and Department of Cell, Developmental, and Integrative Biology (S.J.F.), University of Alabama at Birmingham, Birmingham, Alabama 35294; Cancer Science Institute of Singapore and Department of Pharmacology (P.E.L.), National University of Singapore, Singapore 119077; Department of Radiology (R.P.), Stanford University School of Medicine, Palo Alto, California 94304; Department of Biological Sciences (J.F.L., W.Y.C.), Clemson University, Clemson, South Carolina 29634; and Endocrinology Section (S.J.F.), Medical Service, Veterans Affairs Medical Center, Birmingham, Alabama 35233.
Kurt R ZinnDepartment of Medicine (Y.L., Y.Z., J.J., S.J.F.), Division of Endocrinology, Diabetes, and Metabolism; Department of Radiology (K.R.Z.); and Department of Cell, Developmental, and Integrative Biology (S.J.F.), University of Alabama at Birmingham, Birmingham, Alabama 35294; Cancer Science Institute of Singapore and Department of Pharmacology (P.E.L.), National University of Singapore, Singapore 119077; Department of Radiology (R.P.), Stanford University School of Medicine, Palo Alto, California 94304; Department of Biological Sciences (J.F.L., W.Y.C.), Clemson University, Clemson, South Carolina 29634; and Endocrinology Section (S.J.F.), Medical Service, Veterans Affairs Medical Center, Birmingham, Alabama 35233.
Stuart J FrankDepartment of Medicine (Y.L., Y.Z., J.J., S.J.F.), Division of Endocrinology, Diabetes, and Metabolism; Department of Radiology (K.R.Z.); and Department of Cell, Developmental, and Integrative Biology (S.J.F.), University of Alabama at Birmingham, Birmingham, Alabama 35294; Cancer Science Institute of Singapore and Department of Pharmacology (P.E.L.), National University of Singapore, Singapore 119077; Department of Radiology (R.P.), Stanford University School of Medicine, Palo Alto, California 94304; Department of Biological Sciences (J.F.L., W.Y.C.), Clemson University, Clemson, South Carolina 29634; and Endocrinology Section (S.J.F.), Medical Service, Veterans Affairs Medical Center, Birmingham, Alabama 35233.
Stanford University · USBirmingham VA Medical Center · USClemson University · US

Funding

XRAY CRYSTALLOGRAPHYP30CA013148 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Robert S Welner · 1985 to 2026
$165.9M
University of Alabama at Birmingham's Diabetes Research CenterP30DK079626 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Kirk Michael Habegger · 2013 to 2026
$19.5M
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
NCI NIH HHS P30 CA013148NIDDK NIH HHS P30 DK079626NIDDK NIH HHS R01 DK046395NIDDK NIH HHS R01 DK058259NIDDK NIH HHS R56 DK046395NIDDK NIH HHS R56 DK058259
6 · The paper itself

Abstract

GH receptor (GHR) and prolactin (PRL) receptor (PRLR) are homologous transmembrane cytokine receptors. Each prehomodimerizes and ligand binding activates Janus Kinase 2 (JAK2)-signal transducer and activator of transcription (STAT) signaling pathways by inducing conformational changes within receptor homodimers. In humans, GHR is activated by GH, whereas PRLR is activated by both GH and PRL. We previously devised a split luciferase complementation assay, in which 1 receptor is fused to an N-terminal luciferase (Nluc) fragment, and the other receptor is fused to a C-terminal luciferase (Cluc) fragment. When receptors approximate, luciferase activity (complementation) results. Using this assay, we reported ligand-independent GHR-GHR complementation and GH-induced complementation changes characterized by acute augmentation above basal signal, consistent with induction of conformational changes that bring GHR cytoplasmic tails closer. We also demonstrated association between GHR and PRLR in T47D human breast cancer cells by coimmunoprecipitation, suggesting that, in addition to forming homodimers, these receptors form hetero-assemblages with functional consequences. We now extend these analyses to examine basal and ligand-induced complementation of coexpressed PRLR-Nluc and PRLR-Cluc chimeras and coexpressed GHR-Nluc and PRLR-Cluc chimeras. We find that PRLR-PRLR and GHR-PRLR form specifically interacting ligand-independent assemblages and that either GH or PRL augments PRLR-PRLR complementation, much like the GH-induced changes in GHR-GHR dimers. However, in contrast to the complementation patterns for GHR-GHR or PRLR-PRLR homomers, both GH and PRL caused decline in luciferase activity for GHR-PRLR heteromers. These and other data suggest that GHR and PRLR associate in complexes comprised of GHR-GHR/PRLR-PRLR heteromers consisting of GHR homodimers and PRLR homodimers, rather than GHR-PRLR heterodimers.

Indexed as

Breast NeoplasmsCarrier ProteinsCell Line, TumorFemaleGrowth HormoneHumansImmunoprecipitationJanus Kinase 2LigandsLuciferasesProtein BindingProtein MultimerizationReceptors, ProlactinSignal TransductionCarrier ProteinsGrowth HormoneJAK2 protein, humanJanus Kinase 2LigandsLuciferasesReceptors, Prolactinsomatotropin-binding protein

Identifiers

PMID27003442
PMCPMC4853563
OpenAlexW2303912398

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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.