Neuropoietin, a new IL-6-related cytokine signaling through the ciliary neurotrophic factor receptor

Derouet, Damien; Rousseau, François; Alfonsi, Fabienne; Froger, Josy; Hermann, Jacques; Barbier, Fabien; Perret, David; Diveu, Caroline; Guillet, Catherine; Preisser, Laurence; Dumont, Agnès; Barbado, Maud; Morel, Alain; deLapeyrière, Odile; Gascan, Hugues; Chevalier, Sylvie

doi:10.1073/pnas.0306178101

Cited by 150 publications

(141 citation statements)

References 52 publications

(78 reference statements)

Supporting

Mentioning

135

Contrasting

Unclassified

Order By: Relevance

“…Oncostatin M (OSM) 4 belongs to the family of interleukin (IL)-6-type cytokines, comprising so far nine members: IL-6, IL-11, IL-27, OSM, leukemia inhibitory factor (LIF), ciliary neurotrophic factor, cardiotrophin-1, cardiotrophin-like cytokine and neuropoietin (1)(2)(3). These cytokines are renowned for their pleiotropic functions and have been shown to play important roles in hematopoiesis, inflammation, the acute phase response, bone and heart development, and neurogenesis (1,4).…”

mentioning

confidence: 99%

Box 2 Region of the Oncostatin M Receptor Determines Specificity for Recruitment of Janus Kinases and STAT5 Activation

Hintzen

Evers

Lippok

et al. 2008

Journal of Biological Chemistry

View full text Add to dashboard Cite

Human and murine oncostatin M (OSM) induce their bioactivities through a heterodimeric receptor complex consisting of gp130 and the OSM receptor (OSMR), which initiates a signaling pathway involving Janus kinases (JAKs) and transcription factors of the signal transducers and activators of transcription (STAT) family. In contrast to the signal transducing receptor subunit gp130, the OSMR allows strong activation of STAT5B. The underlying molecular mechanism, however, remained unclear. Here we demonstrate that the human and murine OSM receptors use distinct mechanisms for STAT5B activation. The human receptor contains a STAT5B recruiting tyrosine motif (Tyr 837 /Tyr 839 ) C-terminal to the box 1/2 region, which is absent in the mouse receptor. In contrast, the murine receptor initiates STAT5 activation directly via the receptor bound Janus kinases. Intriguingly, the murine receptor preferentially recruits JAK2, whereas the human receptor seems to have a higher affinity for JAK1. We identify a single amino acid (Phe 820 ) in the human receptor that is responsible for this preference. Exchange by the murine counterpart (Cys 815 ) allows recruitment of JAK2 by the human receptor and consequently activation of STAT5B independently of receptor tyrosine motifs. STAT5B interacts directly with JAK2 only in response to activation of the murine OSMR or the mutated human OSMR. Additionally, we show that OSM-induced STAT1 phosphorylation occurs independently of receptor tyrosine motifs and is mediated directly by Janus kinases, whereas the two C-terminally located tyrosine residues Tyr 917 /Tyr 945 of the OSMR are crucial for STAT3 activation.

show abstract

mentioning

confidence: 99%

Box 2 Region of the Oncostatin M Receptor Determines Specificity for Recruitment of Janus Kinases and STAT5 Activation

Hintzen

Evers

Lippok

et al. 2008

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…The CT-1 related cytokines LIF and IL-6 are expressed in the heart and might compensate for the loss of CT-1. In addition, NP/CT-2 was identified recently as a gp130 family member that is expressed at high levels during embryogenesis [21]. We used real-time PCR to quantify LIF, IL-6 and NP/CT-2 gene expression in adult heart to determine if these cytokines were elevated in CT-1 null mice compared to wild type mice.…”

Section: Resultsmentioning

confidence: 99%

“…A soluble form of the IL-6R is present in plasma, raising the possibility that IL-6 interacts with soluble IL-6R during development to compensate for the absence of CT-1 during development and in the adult heart. The CT-1 related cytokine Neuropoietin/Cardiotropin-2 was identified recently as a gp130 family member that is expressed at high levels during embryogenesis and not present in adult tissues [21]. NP/CT-2 shares a greater degree of similarity with CT-1 than any of the other gp130 family members, and its robust expression during embryogenesis makes it an interesting candidate to compensate for the loss of CT-1 during development.…”

Section: Discussionmentioning

confidence: 99%

The lack of cardiotrophin-1 alters expression of interleukin-6 and leukemia inhibitory factor mRNA but does not impair cardiac injury response

et al. 2006

View full text Add to dashboard Cite

Cardiotrophin-1 (CT-1) was identified as a growth factor for cardiac myocytes, and CT-1 protects myocytes from cell death. Adult CT-1−/− mice exhibit neural deficits including the loss of preganglionic sympathetic neurons, but their autonomic and cardiac parameters have not been examined. We used these mice to determine if the absence of CT-1 or loss of preganglionic sympathetic input altered heart rate, left ventricular pressure, cardiac contractility (dP/dt), or cell death following ischemia-reperfusion. Basal heart rate was increased in CT-1−/− mice, and this difference was abolished by ganglionic block. Left ventricular pressure and dP/dt were unchanged. Dobutamine stimulated similar increases in heart rate and dP/dt in both genotypes, but ventricular pressure was significantly lower in CT-1 nulls. Cardiac expression of interleukin-6 (IL-6) mRNA was increased significantly in CT-1 null mice, while leukemia inhibitory factor (LIF) mRNA was unchanged. Infarct size normalized to area at risk was no different in CT-1 −/− mice (33.8±1.0 % vs. 37.7±3.2 % WT) 24 hours after ischemia-reperfusion. Induction of IL-6 mRNA after infarct was significantly abrogated in CT-1 null mice compared to wild type mice, but LIF mRNA induction remained significant in CT-1 null mice and might contribute to cardiac protection in the absence of CT-1.

show abstract

“…Early cortical progenitors are exposed to CNTF, yet they still produce neurons. 59,60 Similarly, young cortical progenitors were less competent to produce glia than older progenitors when exposed to gliogenic cytokines in culture. 61 Even overexpression of CNTF in young cortical progenitors only generates a slight increase in glial production.…”

Section: Epigenetic Silencing Of Notch Target Genes Restricts Inp Commentioning

confidence: 99%

Opportunities lost and gained: Changes in progenitor competence during nervous system development

Farnsworth

Doe

2017

Neurogenesis

View full text Add to dashboard Cite

During development of the central nervous system, a small pool of stem cells and progenitors generate the vast neural diversity required for neural circuit formation and behavior. Neural stem and progenitor cells often generate different progeny in response to the same signaling cue (e.g. Notch or Hedgehog), including no response at all. How does stem cell competence to respond to signaling cues change over time? Recently, epigenetics particularly chromatin remodeling -has emerged as a powerful mechanism to control stem cell competence. Here we review recent Drosophila and vertebrate literature describing the effect of epigenetic changes on neural stem cell competence.

show abstract

Neuropoietin, a new IL-6-related cytokine signaling through the ciliary neurotrophic factor receptor

Cited by 150 publications

References 52 publications

Box 2 Region of the Oncostatin M Receptor Determines Specificity for Recruitment of Janus Kinases and STAT5 Activation

Box 2 Region of the Oncostatin M Receptor Determines Specificity for Recruitment of Janus Kinases and STAT5 Activation

The lack of cardiotrophin-1 alters expression of interleukin-6 and leukemia inhibitory factor mRNA but does not impair cardiac injury response

Opportunities lost and gained: Changes in progenitor competence during nervous system development

Contact Info

Product

Resources

About