Distinct signal transduction processes by IL-4 and IL-13 and influences from the Q551R variant of the human IL-4 receptor alpha chain
<p>Abstract</p> <p>Background</p> <p>Although IL-4 and IL-13 share the IL-13 receptor, IL-13 exhibits unique functions. To elicit the cellular basis of these differences, signal transduction processes have been compared. Additionally, the role of the IL-4 receptor alpha...
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Online Access: | http://dx.doi.org/10.1186/rr174 |
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doaj-882d63f81b274abea9dfc860526aabc22020-11-24T23:34:45ZengBMCRespiratory Research1465-99212002-08-01312410.1186/rr174Distinct signal transduction processes by IL-4 and IL-13 and influences from the Q551R variant of the human IL-4 receptor alpha chainBraun SandraKruse SusanneDeichmann Klaus A<p>Abstract</p> <p>Background</p> <p>Although IL-4 and IL-13 share the IL-13 receptor, IL-13 exhibits unique functions. To elicit the cellular basis of these differences, signal transduction processes have been compared. Additionally, the role of the IL-4 receptor alpha (IL-4Rα) variant Q551R was investigated.</p> <p>Methods</p> <p>Peripheral blood mononuclear cells from donors were stimulated with IL-4 and IL-13. The phosphorylation status of effector substrates was detected by immunostaining. Binding of SHP-2 to IL-4Rα was investigated by using synthetic peptides.</p> <p>Results</p> <p>SHP-2 bound IL-4Rα synthetic peptide; this binding was reduced in the presence of the R551 variant. Stimulation with IL-4 increased SHP-1 phosphorylation, however, stimulation with IL-13 increased SHP-2 phosphorylation. PI3-kinase phosphorylation was elevated following stimulation with IL-13 in all individuals and with IL-4 only in R551 individuals. Jak1, Tyk2 and IRS-2 signals were reduced after IL-13 stimulation in Q551 individuals. STAT3 phosphorylation was markedly increased in R551 individuals, following stimulation with both IL-4 and IL-13. However, STAT3 was only detected immediately in nuclear extracts from variant individuals after stimulation with IL-13; in wildtype individuals STAT3 was only detected after IL-4 treatment.</p> <p>Conclusion</p> <p>IL-4 and IL-13 appear to promote distinct signal transduction cascades. SHP-1 seems to be predominately activated by IL-4 and to influence the PI3-kinase, in contrast, SHP-2 seems to be predominately activated by IL-13 and to influence Jak1, Tyk2 and IRS-2. Both phosphatases control STAT3. In the presence of the variant R551, SHP-1/2 activation is reduced and signal transduction is altered. STAT3 signaling appears be further regulated on the level of nuclear translocation.</p> http://dx.doi.org/10.1186/rr174asthmaIL-4IL-13SHPSTAT3 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Braun Sandra Kruse Susanne Deichmann Klaus A |
spellingShingle |
Braun Sandra Kruse Susanne Deichmann Klaus A Distinct signal transduction processes by IL-4 and IL-13 and influences from the Q551R variant of the human IL-4 receptor alpha chain Respiratory Research asthma IL-4 IL-13 SHP STAT3 |
author_facet |
Braun Sandra Kruse Susanne Deichmann Klaus A |
author_sort |
Braun Sandra |
title |
Distinct signal transduction processes by IL-4 and IL-13 and influences from the Q551R variant of the human IL-4 receptor alpha chain |
title_short |
Distinct signal transduction processes by IL-4 and IL-13 and influences from the Q551R variant of the human IL-4 receptor alpha chain |
title_full |
Distinct signal transduction processes by IL-4 and IL-13 and influences from the Q551R variant of the human IL-4 receptor alpha chain |
title_fullStr |
Distinct signal transduction processes by IL-4 and IL-13 and influences from the Q551R variant of the human IL-4 receptor alpha chain |
title_full_unstemmed |
Distinct signal transduction processes by IL-4 and IL-13 and influences from the Q551R variant of the human IL-4 receptor alpha chain |
title_sort |
distinct signal transduction processes by il-4 and il-13 and influences from the q551r variant of the human il-4 receptor alpha chain |
publisher |
BMC |
series |
Respiratory Research |
issn |
1465-9921 |
publishDate |
2002-08-01 |
description |
<p>Abstract</p> <p>Background</p> <p>Although IL-4 and IL-13 share the IL-13 receptor, IL-13 exhibits unique functions. To elicit the cellular basis of these differences, signal transduction processes have been compared. Additionally, the role of the IL-4 receptor alpha (IL-4Rα) variant Q551R was investigated.</p> <p>Methods</p> <p>Peripheral blood mononuclear cells from donors were stimulated with IL-4 and IL-13. The phosphorylation status of effector substrates was detected by immunostaining. Binding of SHP-2 to IL-4Rα was investigated by using synthetic peptides.</p> <p>Results</p> <p>SHP-2 bound IL-4Rα synthetic peptide; this binding was reduced in the presence of the R551 variant. Stimulation with IL-4 increased SHP-1 phosphorylation, however, stimulation with IL-13 increased SHP-2 phosphorylation. PI3-kinase phosphorylation was elevated following stimulation with IL-13 in all individuals and with IL-4 only in R551 individuals. Jak1, Tyk2 and IRS-2 signals were reduced after IL-13 stimulation in Q551 individuals. STAT3 phosphorylation was markedly increased in R551 individuals, following stimulation with both IL-4 and IL-13. However, STAT3 was only detected immediately in nuclear extracts from variant individuals after stimulation with IL-13; in wildtype individuals STAT3 was only detected after IL-4 treatment.</p> <p>Conclusion</p> <p>IL-4 and IL-13 appear to promote distinct signal transduction cascades. SHP-1 seems to be predominately activated by IL-4 and to influence the PI3-kinase, in contrast, SHP-2 seems to be predominately activated by IL-13 and to influence Jak1, Tyk2 and IRS-2. Both phosphatases control STAT3. In the presence of the variant R551, SHP-1/2 activation is reduced and signal transduction is altered. STAT3 signaling appears be further regulated on the level of nuclear translocation.</p> |
topic |
asthma IL-4 IL-13 SHP STAT3 |
url |
http://dx.doi.org/10.1186/rr174 |
work_keys_str_mv |
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