Homodimerization of IL‐2 receptor β chain is necessary and sufficient to activate Jak2 and dowstream signaling pathways

Ferrag, Fatima; Pezet, Alain; Chiarenza, Andrea; Buteau, Hélène; Nelson, Brad H.; Goffin, Vincent; Kelly, P. A.

doi:10.1016/s0014-5793(97)01529-9

Cited by 16 publications

(14 citation statements)

References 45 publications

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“…When transfected alone, IL-2Rβ forms a homodimer able to bind IL-2 [51]. Complexes of IL-2Rβ, formed by the intra-cellular domain of IL-2Rβ fused to the extracellular domain of c-kit, have been shown to activate the Jak2 pathway [52] whereas IL-2 receptor signalling through the conventional α/β/γ complex leads to phosphorylation of Jak1 and 3. Similar experiments have not been performed with IL-15, which is synthesized by decidual cells and thus more likely than IL-2 to stimulate the trophoblast IL-2Rβ in vivo .…”

Section: Discussionmentioning

confidence: 99%

Genome-wide expression profile of first trimester villous and extravillous human trophoblast cells

et al. 2011

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We have examined the transcriptional changes associated with differentiation from villous to extravillous trophoblast using a whole genome microarray. Villous trophoblast (VT) is in contact with maternal blood and mediates nutrient exchange whereas extravillous trophoblast (EVT) invades the decidua and remodels uterine arteries. Using highly purified first trimester trophoblast we identified over 3000 transcripts that are differentially expressed. Many of these transcripts represent novel functions and pathways that show co-ordinated up-regulation in VT or EVT. In addition we identify new players in established functions such as migration, immune modulation and cytokine or angiogenic factor secretion by EVT. The transition from VT to EVT is also characterised by alterations in transcription factors such as STAT4 and IRF9, which may co-ordinate these changes. Transcripts encoding several members of the immunoglobulin-superfamily, which are normally expressed on leukocytes, were highly transcribed in EVT but not expressed as protein, indicating specific control of translation in EVT. Interactions of trophoblast with decidual leukocytes are involved in regulating EVT invasion. We show that decidual T-cells, macrophages and NK cells express the inhibitory collagen receptor LAIR-1 and that EVT secrete LAIR-2, which can block this interaction. This represents a new mechanism by which EVT can modulate leukocyte function in the decidua. Since LAIR-2 is detectable in the urine of pregnant, but not non-pregnant women, trophoblast-derived LAIR-2 may also have systemic effects during pregnancy.

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Section: Discussionmentioning

confidence: 99%

Genome-wide expression profile of first trimester villous and extravillous human trophoblast cells

et al. 2011

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“…[20][21][22][23] Previous studies suggested that ␥c-related receptors including IL-2R␤ chain and IL-4R␣ chain could activate janus-activated kinases (JAKs) to some extent in the presence of the extracellular domain of ␥c, independent of the cytoplasmic domain of ␥c. 24,25 Thus, in order to block the signaling through ␥c-related cytokine receptors more completely, we made NOD/SCID mice harboring complete null mutation of ␥c 16 (the NOD/SCID/IL2r␥ null strain). By using NOD/SCID/IL2r␥ null newborns, we successfully reconstituted myeloerythroid as well as lymphoid maturation by injecting human CB or highly-enriched CB HSCs at a high efficiency.…”

Section: Introductionmentioning

confidence: 99%

Development of functional human blood and immune systems in NOD/SCID/IL2 receptor γ chainnull mice

Ishikawa

Yasukawa

Lyons

et al. 2005

Blood

846

790

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“…he pleiotropic actions of the somatolactogenic hormone prolactin (PRL) are mediated by signaling through the prolactin receptor, a member of the type I family of cytokine receptors (1)(2)(3). Upon ligand binding and dimerization of the receptor, several signaling cascades are activated, including Ras-Raf, Fyn-Vav and Jak2-Stat5 (4-7).…”

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confidence: 99%

The intranuclear prolactin/cyclophilin B complex as a transcriptional inducer

Rycyzyn

Clevenger

2002

Proc. Natl. Acad. Sci. U.S.A.

141

124

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The nuclear translocation of peptide hormones, such as the somatolactogenic hormone prolactin, after receptor internalization has been widely reported. Prolactin has been demonstrated to interact with cyclophilin B, a member of the immunophilin family of proteins. Cyclophilin B interaction with prolactin potentiated prolactin-induced proliferation, cell growth, and the nuclear retrotransport of prolactin. These effects could be abrogated by the removal of the peptidyl-prolyl isomerase activity of cyclophilin B. Our findings indicate that the intranuclear prolactin͞cyclophilin B complex acts as a transcriptional inducer by interacting directly with Stat5, resulting in the removal of the Stat-repressor protein inhibitor of activated Stat 3 (PIAS3), thereby enhancing Stat5 DNA-binding activity and prolactin-induced, Stat5-mediated gene expression.T he pleiotropic actions of the somatolactogenic hormone prolactin (PRL) are mediated by signaling through the prolactin receptor, a member of the type I family of cytokine receptors (1-3). Upon ligand binding and dimerization of the receptor, several signaling cascades are activated, including Ras-Raf, Fyn-Vav and Jak2-Stat5 (4-7). Activated Jak2 phosphorylates Stat5 on tyrosine residues, inducing Stat5 dimerization and translocation to the nucleus (8). Intranuclear Stat5 binds to consensus Stat5 response elements, resulting in the transactivation of numerous PRL-specific genes, of which ␤-casein is the most extensively studied (9). This Stat5 transcriptional activation can be cooperatively enhanced by the glucocorticoid receptor (GR) and C͞EBP␤ (10-12).While the above-mentioned pathways are all associated with PRL-induced signaling, activation of the PRL receptor is also associated with ligand internalization via an endosomal-like pathway across the endoplasmic reticulum (ER) and nuclear envelopes (13,14). The phenomenon of protein retrotransport was initially characterized through the study of retrotranslocated viral and bacterial proteins and peptides destined for presentation on the major histocompatibility complex (15-18). These studies revealed that protein retrotransport depends on transport through the protein-conducting channel formed by the Sec61 complex in the ER membrane. Electron microscopy studies employing colloidal gold-labeled PRL demonstrated that upon ligand internalization into endosomes, approximately 90% of the internalized PRL either remained within the endosome or was degraded. However, the remaining 10% was detected as passing from the endosome through multivesicular bodies and the Golgi͞ER to arrive in the nucleus within 2 h poststimulation (13). The functional significance of nuclear PRL was demonstrated by the finding that a nuclear-targeted construct of PRL containing the simian virus 40 large T antigen nuclear localization sequence provided a necessary comitogenic stimulus for IL-2-driven growth (19). The nuclear retrotransport and potential action of peptide hormones and growth factors is widespread, as epidermal growth factor, insulin, grow...

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Homodimerization of IL‐2 receptor β chain is necessary and sufficient to activate Jak2 and dowstream signaling pathways

Cited by 16 publications

References 45 publications

Genome-wide expression profile of first trimester villous and extravillous human trophoblast cells

Genome-wide expression profile of first trimester villous and extravillous human trophoblast cells

Development of functional human blood and immune systems in NOD/SCID/IL2 receptor γ chainnull mice

The intranuclear prolactin/cyclophilin B complex as a transcriptional inducer

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