ArticlePloS one2011
Jak2 is a negative regulator of ubiquitin-dependent endocytosis of the growth hormone receptor.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Small molecules to regulate the GH/IGF1 axis by inhibiting the growth hormone receptor synthesis.Frontiers in endocrinology · 2022Article
- Growth Hormone Receptor Regulation in Cancer and Chronic Diseases.Frontiers in endocrinology · 2020Review
- Ruxolitinib sensitizes ovarian cancer to reduced dose Taxol, limits tumor growth and improves survival in immune competent mice.Oncotarget · 2017Article
- Cytokine Receptor Endocytosis: New Kinase Activity-Dependent and -Independent Roles of PI3K.Frontiers in endocrinology · 2017Review
- Fos-Zippered GH Receptor Cytosolic Tails Act as Jak2 Substrates and Signal Transducers.Molecular endocrinology (Baltimore, Md.) · 2016Article
- Multimeric growth hormone receptor complexes serve as signaling platforms.The Journal of biological chemistry · 2014Article
- Eliminative signaling by Janus kinases: role in the downregulation of associated receptors.Journal of cellular biochemistry · 2014Review
- Article
- The ING1a tumor suppressor regulates endocytosis to induce cellular senescence via the Rb-E2F pathway.PLoS biology · 2013Article
- Ubc13 and COOH terminus of Hsp70-interacting protein (CHIP) are required for growth hormone receptor endocytosis.The Journal of biological chemistry · 2012Article
- Growth hormone-induced JAK2 signaling and GH receptor down-regulation: role of GH receptor intracellular domain tyrosine residues.Endocrinology · 2012Article
- βTrCP controls GH receptor degradation via two different motifs.Molecular endocrinology (Baltimore, Md.) · 2012Article
- Identification of JAK2 as a mediator of FIP1L1-PDGFRA-induced eosinophil growth and function in CEL.PloS one · 2012Article
- Article
- AAK1-like: A putative pseudokinase with potential roles in cargo uptake in bloodstream form Trypanosoma brucei parasites.The Journal of eukaryotic microbiologyArticle
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLength and intensity of signal transduction via cytokine receptors is precisely regulated. Degradation of certain cytokine receptors is mediated by the ubiquitin ligase SCF(βTrCP). In several instances, Janus kinase (Jak) family members can stabilise their cognate cytokine receptors at the cell surface. PRINCIPAL
findingsIn this study we show in Hek293 cells that Jak2 binding to the growth hormone receptor prevents endocytosis in a non-catalytic manner. Following receptor activation, the detachment of phosphorylated Jak2 induces down-regulation of the growth hormone receptor by SCF(βTrCP). Using γ2A human fibroblast cells we show that both growth hormone-induced and constitutive growth hormone receptor endocytosis depend on the same factors, strongly suggesting that the modes of endocytosis are identical. Different Jak2 RNA levels in HepG2, IM9 and Hek293 cells indicate the importance of cellular concentration on growth hormone receptor function. Both Jak2 and βTrCP bind to neighbouring linear motifs in the growth hormone receptor tail without the requirement of modifications, indicating that growth hormone sensitivity is regulated by the cellular level of non-committed Jak2. CONCLUSIONS/SIGNIFICANCE: As signal transduction of many cytokine receptors depends on Jak2, the study suggests an integrative role of Jak2 in cytokine responses based on its enzyme activity as well as its stabilising properties towards the receptors.
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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.