ArticleThe Journal of biological chemistry2014
Multimeric growth hormone receptor complexes serve as signaling platforms.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- Distinct Assemblies of Heterodimeric Cytokine Receptors Govern Stemness Programs in Leukemia.Cancer discovery · 2023Article
- Small molecules to regulate the GH/IGF1 axis by inhibiting the growth hormone receptor synthesis.Frontiers in endocrinology · 2022Article
- Classical and novel GH receptor signaling pathways.Molecular and cellular endocrinology · 2020Review
- Growth Hormone Receptor Regulation in Cancer and Chronic Diseases.Frontiers in endocrinology · 2020Review
- Whole Genome Messenger RNA Profiling Identifies a Novel Signature to Predict Gastric Cancer Survival.Clinical and translational gastroenterology · 2019Article
- Subdomain 2, Not the Transmembrane Domain, Determines the Dimerization Partner of Growth Hormone Receptor and Prolactin Receptor.Endocrinology · 2017Article
- Article
- GHR/PRLR Heteromultimer Is Composed of GHR Homodimers and PRLR Homodimers.Molecular endocrinology (Baltimore, Md.) · 2016Article
- Fos-Zippered GH Receptor Cytosolic Tails Act as Jak2 Substrates and Signal Transducers.Molecular endocrinology (Baltimore, Md.) · 2016Article
- A Decade of Boon or Burden: What Has the CHIP Ever Done for Cellular Protein Quality Control Mechanism Implicated in Neurodegeneration and Aging?Frontiers in molecular neuroscience · 2016Review
- GH/STAT5 signaling during the growth period in livers of mice overexpressing GH.Journal of molecular endocrinology · 2015Article
- Dynamic analysis of GH receptor conformational changes by split luciferase complementation.Molecular endocrinology (Baltimore, Md.) · 2014Article
- Growth hormone receptor inhibition decreases the growth and metastasis of pancreatic ductal adenocarcinoma.Experimental & molecular medicine · 2014Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Growth hormone (GH) signaling is required for promoting longitudinal body growth, stem cell activation, differentiation, and survival and for regulation of metabolism. Failure to adequately regulate GH signaling leads to disease: excessive GH signaling has been connected to cancer, and GH insensitivity has been reported in cachexia patients. Since its discovery in 1989, the receptor has served a pivotal role as the prototype cytokine receptor both structurally and functionally. Phosphorylation and ubiquitylation regulate the GH receptor (GHR) at the cell surface: two ubiquitin ligases (SCF(βTrCP2) and CHIP) determine the GH responsiveness of cells by controlling its endocytosis, whereas JAK2 initiates the JAK/STAT pathway. We used blue native electrophoresis to identify phosphorylated and ubiquitylated receptor intermediates. We show that GHRs occur as ∼500-kDa complexes that dimerize into active ∼900-kDa complexes upon GH binding. The dimerized complexes act as platforms for transient interaction with JAK2 and ubiquitin ligases. If GH and receptors are made in the same cell (autocrine mode), only limited numbers of ∼900-kDa complexes are formed. The experiments reveal the dynamic changes in post-translational modifications during GH-induced signaling events and show that relatively simple cytokine receptors like GHRs are able to form higher order protein complexes. Insight in the complex formation of cytokine receptors is crucially important for engineering cytokines that control ligand-induced cell responses and for generating a new class of therapeutic agents for a wide range of diseases.
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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.