scholarly journals Suppressor of Cytokine Signaling 6 (SOCS6) Negatively Regulates Flt3 Signal Transduction through Direct Binding to Phosphorylated Tyrosines 591 and 919 of Flt3

2012 ◽  
Vol 287 (43) ◽  
pp. 36509-36517 ◽  
Author(s):  
Julhash U. Kazi ◽  
Jianmin Sun ◽  
Bengt Phung ◽  
Fahad Zadjali ◽  
Amilcar Flores-Morales ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Direct Binding

scholarly journals Angiotensin II (AngII) induces the expression of suppressor of cytokine signaling (SOCS)-3 in rat hypothalamus - a mechanism for desensitization of AngII signaling

2004 ◽  
Vol 181 (1) ◽  
pp. 117-128 ◽  
Author(s):  
MA Torsoni ◽  
JB Carvalheira ◽  
VC Calegari ◽  
RM Bezerra ◽  
MJ Saad ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Signal Transduction ◽  
Angiotensin Ii ◽  
Antisense Oligonucleotide ◽  
Inhibitory Effect ◽  
Cytokine Signaling ◽  
Signal Transduction Pathways ◽  
Angiotensin Receptor ◽  
Suppressor Of Cytokine Signaling ◽  
Water Ingestion

Angiotensin II exerts a potent dypsogenic stimulus on the hypothalamus, which contributes to its centrally mediated participation in the control of water balance and blood pressure. Repetitive intracerebroventricular (i.c.v.) injections of angiotensin II lead to a loss of effect characterized as physiological desensitization to the peptide's action. In the present study, we demonstrate that angiotensin II induces the expression of suppressor of cytokine signaling (SOCS)-3 via angiotensin receptor 1 (AT1) and JAK-2, mostly located at the median preoptic lateral and anterodorsal preoptic nuclei. SOCS-3 produces an inhibitory effect upon the signal transduction pathways of several cytokines and hormones that employ members of the JAK/STAT families as intermediaries. The partial inhibition of SOCS-3 translation by antisense oligonucleotide was sufficient to significantly reduce the refractoriness of repetitive i.c.v. angiotensin II injections, as evaluated by water ingestion. Thus, by acting through AT1 on the hypothalamus, angiotensin II induces the expression of SOCS-3 which, in turn, blocks further activation of the pathway and consequently leads to desensitization to angiotensin II stimuli concerning its dypsogenic effect.

scholarly journals Suppressor of Cytokine Signaling-3 Inhibits Interleukin-1 Signaling by Targeting the TRAF-6/TAK1 Complex

2006 ◽  
Vol 20 (7) ◽  
pp. 1587-1596 ◽  
Author(s):  
Helle Frobøse ◽  
Sif Groth Rønn ◽  
Peter E. Heding ◽  
Heidi Mendoza ◽  
Philip Cohen ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Interleukin 1 ◽  
Cytokine Signaling ◽  
Nuclear Factor ◽  
Tnf Receptor ◽  
Suppressor Of Cytokine Signaling ◽  
Signaling Complex ◽  
Nuclear Factor Κ B ◽  
Erk Kinase

Abstract IL-1 plays a major role in inflammation and autoimmunity through activation of nuclear factor κ B (NFκB) and MAPKs. Although a great deal is known about the mechanism of activation of NFκB and MAPKs by IL-1, much less is known about the down-regulation of this pathway. Suppressor of cytokine signaling (SOCS)-3 was shown to inhibit IL-1-induced transcription and activation of NFκB and the MAPKs JNK and p38, but the mechanism is unknown. We show here that SOCS-3 inhibits NFκB-dependent transcription induced by overexpression of the upstream IL-1 signaling molecules MyD88, IL-1R-activated kinase 1, TNF receptor-associated factor (TRAF)6, and TGFβ-activated kinase (TAK)1, but not when the MAP3K MAPK/ERK kinase kinase-1 is used instead of TAK1, indicating that the target for SOCS-3 is the TRAF6/TAK1 signaling complex. By coimmunoprecipitation, it was shown that SOCS-3 inhibited the association between TRAF6 and TAK1 and that SOCS-3 coimmunoprecipitated with TAK1 and TRAF6. Furthermore, SOCS-3 inhibited the IL-1-induced catalytic activity of TAK1. Because ubiquitination of TRAF6 is required for activation of TAK1, we analyzed the role of SOCS-3 on TRAF6 ubiquitination and found that SOCS-3 inhibited ubiquitin modification of TRAF6. These results indicate that SOCS-3 inhibits IL-1 signal transduction by inhibiting ubiquitination of TRAF6, thus preventing association and activation of TAK1.

scholarly journals Dual effects of suppressor of cytokine signaling (SOCS-2) on growth hormone signal transduction

FEBS Letters ◽  
1999 ◽  
Vol 453 (1-2) ◽  
pp. 63-66 ◽  
Author(s):  
Hélène Favre ◽  
Aurélie Benhamou ◽  
Joelle Finidori ◽  
Paul A. Kelly ◽  
Marc Edery
Keyword(s):  
Signal Transduction ◽  
Growth Hormone ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling

scholarly journals Cytokine signal transduction is suppressed in preselection double-positive thymocytes and restored by positive selection

2006 ◽  
Vol 203 (1) ◽  
pp. 165-175 ◽  
Author(s):  
Qing Yu ◽  
Jung-Hyun Park ◽  
Loretta L. Doan ◽  
Batu Erman ◽  
Lionel Feigenbaum ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Positive Selection ◽  
T Cell Receptor ◽  
High Surface ◽  
Cell Receptor ◽  
Surface Expression ◽  
Small Cell ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Double Positive

Death by neglect requires that CD4+8+ double-positive (DP) thymocytes avoid cytokine-mediated survival signals, which is presumably why DP thymocytes normally extinguish IL-7R gene expression. We report that DP thymocytes before positive selection (preselection DP thymocytes) fail to transduce IL-7 signals even when they express high levels of transgenic IL-7R on their surface, because IL-7R signal transduction is actively suppressed in preselection DP thymocytes by suppressor of cytokine signaling (SOCS)–1. SOCS-1 is highly expressed in preselection DP thymocytes, but it is down-regulated by T cell receptor–mediated positive selection signals. Interestingly, we found that the uniquely small cell volume of DP thymocytes is largely the result of absent IL-7 signaling in preselection DP thymocytes. We also report that, contrary to current concepts, preselection DP thymocytes express high levels of endogenously encoded IL-4Rs. However, their ability to transduce cytokine signals is similarly suppressed by SOCS-1. Thus, despite high surface expression of transgenic or endogenous cytokine receptors, cytokine signal transduction is actively suppressed in preselection DP thymocytes until it is restored by positive selection.

Die Aktivierung der MKK6/p38 Kaskade ist essentiell für die Stabilisierung der Suppressor of Cytokine Signaling 3 mRNA durch TNF-alpha

2006 ◽  
Vol 44 (01) ◽  
Author(s):  
C Ehlting ◽  
F Schaper ◽  
ED Brenndörfer ◽  
PC Heinrich ◽  
D Häussinger ◽  
...  
Keyword(s):  
Tnf Alpha ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling
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