Matches in SemOpenAlex for { <https://semopenalex.org/work/W2027958908> ?p ?o ?g. }
- W2027958908 endingPage "8701" @default.
- W2027958908 startingPage "8691" @default.
- W2027958908 abstract "Interleukin (IL)-7 is the main homeostatic regulator of CD4 T-lymphocytes (helper) at both central and peripheral levels. Upon activation by IL-7, several signaling pathways, mainly JAK/STAT, PI3K/Akt and MAPK, induce the expression of genes involved in T-cell differentiation, activation, and proliferation. We have analyzed the early events of CD4 T-cell activation by IL-7. We have shown that IL-7 in the first few min induces the formation of cholesterol-enriched membrane microdomains that compartmentalize its activated receptor and initiate its anchoring to the cytoskeleton, supporting the formation of the signaling complex, the signalosome, on the IL-7 receptor cytoplasmic domains. Here we describe by stimulated emission depletion microscopy the key roles played by membrane microdomains and cytoskeleton transient organization in the IL-7-regulated JAK/STAT signaling pathway. We image phospho-STAT5 and cytoskeleton components along IL-7 activation kinetics using appropriate inhibitors. We show that lipid raft inhibitors delay and reduce IL-7-induced JAK1 and JAK3 phosphorylation. Drug-induced disassembly of the cytoskeleton inhibits phospho-STAT5 formation, transport, and translocation into the nucleus that controls the transcription of genes involved in T-cell activation and proliferation. We fit together the results of these quantitative analyses and propose the following mechanism. Activated IL-7 receptors embedded in membrane microdomains induce actin-microfilament meshwork formation, anchoring microtubules that grow radially from rafted receptors to the nuclear membrane. STAT5 phosphorylated by signalosomes are loaded on kinesins and glide along the microtubules across the cytoplasm to reach the nucleus 2 min after IL-7 stimulation. Radial microtubules disappear 15 min later, while transversal microtubules, independent of phospho-STAT5 transport, begin to bud from the microtubule organization center. Interleukin (IL)-7 is the main homeostatic regulator of CD4 T-lymphocytes (helper) at both central and peripheral levels. Upon activation by IL-7, several signaling pathways, mainly JAK/STAT, PI3K/Akt and MAPK, induce the expression of genes involved in T-cell differentiation, activation, and proliferation. We have analyzed the early events of CD4 T-cell activation by IL-7. We have shown that IL-7 in the first few min induces the formation of cholesterol-enriched membrane microdomains that compartmentalize its activated receptor and initiate its anchoring to the cytoskeleton, supporting the formation of the signaling complex, the signalosome, on the IL-7 receptor cytoplasmic domains. Here we describe by stimulated emission depletion microscopy the key roles played by membrane microdomains and cytoskeleton transient organization in the IL-7-regulated JAK/STAT signaling pathway. We image phospho-STAT5 and cytoskeleton components along IL-7 activation kinetics using appropriate inhibitors. We show that lipid raft inhibitors delay and reduce IL-7-induced JAK1 and JAK3 phosphorylation. Drug-induced disassembly of the cytoskeleton inhibits phospho-STAT5 formation, transport, and translocation into the nucleus that controls the transcription of genes involved in T-cell activation and proliferation. We fit together the results of these quantitative analyses and propose the following mechanism. Activated IL-7 receptors embedded in membrane microdomains induce actin-microfilament meshwork formation, anchoring microtubules that grow radially from rafted receptors to the nuclear membrane. STAT5 phosphorylated by signalosomes are loaded on kinesins and glide along the microtubules across the cytoplasm to reach the nucleus 2 min after IL-7 stimulation. Radial microtubules disappear 15 min later, while transversal microtubules, independent of phospho-STAT5 transport, begin to bud from the microtubule organization center. Correction: Membrane microdomains and cytoskeleton organization shape and regulate the IL-7 receptor signalosome in human CD4 T-cells.Journal of Biological ChemistryVol. 294Issue 13PreviewVOLUME 288 (2013) PAGES 8691–8701 Full-Text PDF Open Access" @default.
- W2027958908 created "2016-06-24" @default.
- W2027958908 creator A5018281158 @default.
- W2027958908 creator A5021522442 @default.
- W2027958908 creator A5022379929 @default.
- W2027958908 creator A5037802763 @default.
- W2027958908 creator A5038506856 @default.
- W2027958908 creator A5052754853 @default.
- W2027958908 creator A5057563015 @default.
- W2027958908 creator A5059979662 @default.
- W2027958908 creator A5078662289 @default.
- W2027958908 date "2013-03-01" @default.
- W2027958908 modified "2023-10-12" @default.
- W2027958908 title "Membrane Microdomains and Cytoskeleton Organization Shape and Regulate the IL-7 Receptor Signalosome in Human CD4 T-cells" @default.
- W2027958908 cites W1499854106 @default.
- W2027958908 cites W1676499072 @default.
- W2027958908 cites W1678155885 @default.
- W2027958908 cites W1936814681 @default.
- W2027958908 cites W1965487513 @default.
- W2027958908 cites W1972527945 @default.
- W2027958908 cites W1974368689 @default.
- W2027958908 cites W1979026253 @default.
- W2027958908 cites W1981916955 @default.
- W2027958908 cites W1983823640 @default.
- W2027958908 cites W1985501881 @default.
- W2027958908 cites W1986114734 @default.
- W2027958908 cites W1989054935 @default.
- W2027958908 cites W1990846870 @default.
- W2027958908 cites W1994844769 @default.
- W2027958908 cites W2003838317 @default.
- W2027958908 cites W2011825215 @default.
- W2027958908 cites W2050520078 @default.
- W2027958908 cites W2055560543 @default.
- W2027958908 cites W2058363464 @default.
- W2027958908 cites W2062738834 @default.
- W2027958908 cites W2070487296 @default.
- W2027958908 cites W2073848442 @default.
- W2027958908 cites W2082203876 @default.
- W2027958908 cites W2086121828 @default.
- W2027958908 cites W2096679660 @default.
- W2027958908 cites W2103944364 @default.
- W2027958908 cites W2110358604 @default.
- W2027958908 cites W2115737236 @default.
- W2027958908 cites W2124511577 @default.
- W2027958908 cites W2134135483 @default.
- W2027958908 cites W2135416763 @default.
- W2027958908 cites W2147321931 @default.
- W2027958908 cites W2148710439 @default.
- W2027958908 cites W2151298994 @default.
- W2027958908 cites W2153011776 @default.
- W2027958908 cites W4211203651 @default.
- W2027958908 doi "https://doi.org/10.1074/jbc.m113.449918" @default.
- W2027958908 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6442037" @default.
- W2027958908 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30926760" @default.
- W2027958908 hasPublicationYear "2013" @default.
- W2027958908 type Work @default.
- W2027958908 sameAs 2027958908 @default.
- W2027958908 citedByCount "29" @default.
- W2027958908 countsByYear W20279589082013 @default.
- W2027958908 countsByYear W20279589082014 @default.
- W2027958908 countsByYear W20279589082015 @default.
- W2027958908 countsByYear W20279589082016 @default.
- W2027958908 countsByYear W20279589082018 @default.
- W2027958908 countsByYear W20279589082019 @default.
- W2027958908 countsByYear W20279589082020 @default.
- W2027958908 countsByYear W20279589082021 @default.
- W2027958908 countsByYear W20279589082022 @default.
- W2027958908 countsByYear W20279589082023 @default.
- W2027958908 crossrefType "journal-article" @default.
- W2027958908 hasAuthorship W2027958908A5018281158 @default.
- W2027958908 hasAuthorship W2027958908A5021522442 @default.
- W2027958908 hasAuthorship W2027958908A5022379929 @default.
- W2027958908 hasAuthorship W2027958908A5037802763 @default.
- W2027958908 hasAuthorship W2027958908A5038506856 @default.
- W2027958908 hasAuthorship W2027958908A5052754853 @default.
- W2027958908 hasAuthorship W2027958908A5057563015 @default.
- W2027958908 hasAuthorship W2027958908A5059979662 @default.
- W2027958908 hasAuthorship W2027958908A5078662289 @default.
- W2027958908 hasBestOaLocation W20279589081 @default.
- W2027958908 hasConcept C125705527 @default.
- W2027958908 hasConcept C142669718 @default.
- W2027958908 hasConcept C1491633281 @default.
- W2027958908 hasConcept C2993400109 @default.
- W2027958908 hasConcept C3620293 @default.
- W2027958908 hasConcept C55493867 @default.
- W2027958908 hasConcept C62478195 @default.
- W2027958908 hasConcept C86803240 @default.
- W2027958908 hasConcept C95444343 @default.
- W2027958908 hasConceptScore W2027958908C125705527 @default.
- W2027958908 hasConceptScore W2027958908C142669718 @default.
- W2027958908 hasConceptScore W2027958908C1491633281 @default.
- W2027958908 hasConceptScore W2027958908C2993400109 @default.
- W2027958908 hasConceptScore W2027958908C3620293 @default.
- W2027958908 hasConceptScore W2027958908C55493867 @default.
- W2027958908 hasConceptScore W2027958908C62478195 @default.
- W2027958908 hasConceptScore W2027958908C86803240 @default.
- W2027958908 hasConceptScore W2027958908C95444343 @default.
- W2027958908 hasIssue "12" @default.