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LEP — SOCS3
Pathways - manually collected, often from reviews:
-
NCI Pathway Database Signaling events mediated by PTP1B:
Leptin (LEP)
→
SOCS3 (SOCS3)
(modification, collaborate)
Bjørbaek et al., J Biol Chem 1999, Tartaglia et al., Cell 1995*
Evidence: physical interaction, other species
-
NCI Pathway Database Signaling events mediated by PTP1B:
SOCS3 (SOCS3)
→
Jak2/Leptin Receptor/Leptin complex (JAK2-LEPR-LEP)
(modification, inhibits)
Bjørbaek et al., J Biol Chem 1999, Tartaglia et al., Cell 1995*
Evidence: physical interaction, other species
-
Reactome Reaction:
LEP
→
SOCS3
(reaction)
-
Reactome Reaction:
LEP
→
SOCS3
(indirect_complex)
Text-mined interactions from Literome
Elias et al., Neuron 1999
(Body Weight) :
In contrast,
leptin induced both Fos and
SOCS-3 expression in POMC neurons, many of which also innervated the LHA
Bjørbaek et al., J Biol Chem 1999
:
The
role of
SOCS-3 in
leptin signaling and leptin resistance ... However, little is known about the
regulation of
SOCS-3 expression by
leptin and the mechanism by which SOCS-3 inhibits leptin action
Elmquist et al., Physiol Behav 2001
(Body Weight) :
In contrast,
leptin induced both Fos and
SOCS-3 expression in POMC neurons, many of which also innervated the LHA
Elmquist et al., Int J Obes Relat Metab Disord 2001
:
In contrast,
leptin induced
SOCS-3 expression in neuropeptide Y (NPY) neurons but not Fos, suggesting that leptin acts differentially on NPY and POMC cells
Proulx et al., Endocrinology 2002
(Weight Gain) :
In the arcuate nucleus (ARC), acute
leptin increased
SOCS-3 and POMC mRNA levels, but decreased NPY mRNA levels in the rostral part of ARC
Tups et al., Endocrinology 2004
(Body Weight) :
Our results suggest that the development of leptin resistance in LD-acclimated hamsters involves
SOCS3 mediated suppression of
leptin signaling in the arcuate nucleus ... Increased
SOCS3 expression in LD hamsters is
independent of body fat and serum
leptin levels, suggesting that the photoperiod is able to trigger the biannual reversible switch in leptin sensitivity
Mori et al., Nat Med 2004
(Insulin Resistance...) :
Our study demonstrates the negative regulatory
role of
Socs3 in
leptin signaling in vivo, and thus suppression of Socs3 in the brain is a potential therapy for leptin-resistance in obesity
Münzberg et al., Endocrinology 2004
(Body Weight...) :
We found that the level of
suppressor of cytokine signaling 3 ( SOCS-3 ), an
inhibitor of
leptin signaling, is specifically increased in the ARC of DIO mice
Laubner et al., Diabetes 2005
(Insulinoma...) :
Inhibition of preproinsulin gene expression by
leptin induction of
suppressor of cytokine signaling 3 in pancreatic beta-cells ...
Leptin also
induced mRNA expression of the JAK-STAT inhibitor suppressor of cytokine signaling
(SOCS)3 in INS-1 beta-cells and human pancreatic islets in vitro and in pancreatic islets of ob/ob mice in vivo ... Transcriptional
activation of the rat
SOCS3 promoter by
leptin was observed with concomitant leptin induced STAT3 and STAT5b DNA binding to specific promoter regions
Mitchell et al., J Endocrinol 2006
(Body Weight) :
SOCS3 mRNA induction in
response to
leptin was lower in the Lou/C rat
Eguchi et al., Mol Cell Endocrinol 2007
:
Regulation of
SOCS-3 expression by
leptin and its co-localization with insulin receptor in rat skeletal muscle cells ... In summary,
leptin induced
SOCS-3 expression and its association with the insulin receptor in rat skeletal muscle cells but functional significance of this increase was not apparent upon measuring glucose uptake
Boyle et al., J Reprod Immunol 2008
:
The creation of mice with conditional deletion of SOCS3 in different tissues has also uncovered critical
roles for
SOCS3 in the regulation of IL-6, G-CSF and
leptin signalling
Ahmed et al., Vet J 2008
:
Leptin alone
increased only
SOCS3 mRNA expression
Zieba et al., J Endocrinol 2008
:
However, unlike changes in melatonin, circulating PRL decreased ( P < 0.001 ) in response to leptin during LD. Semi-quantitative PCR revealed that
leptin increased ( P < 0.001 )
SOCS-3 expression in the MBH region during LD in a dose dependent manner
Lubis et al., Acta Med Indones 2008
(Obesity) :
SOCS-3 expression is
induced by
leptin and SOCS-3 activation will inhibit STAT3 phosphorylation which is important in signal transmission on leptin receptors
Silva et al., J Dairy Sci 2008
:
Leptin enhanced
SOCS-3 expression in IGF-I treated quarters but did not alter SOCS-1 or SOCS-5 expression
Zhang et al., Endocrinology 2008
(Body Weight) :
These results suggest that
Socs3 in SF1 neurons negatively
regulates leptin signaling and plays important roles in mediating leptin sensitivity, glucose homeostasis, and energy expenditure
Schulz et al., Biol Reprod 2009
:
Leptin stimulated the phosphorylation of MEK ( MAP2K1 ) but not signal transducer and activator of transcription 3 ( STAT3 ) in the cultures,
increased the concentration of the
suppressor of cytokine signaling 3 ( SOCS3 ) protein, and upregulated metalloproteinase activity
Liu et al., Mol Biol Rep 2010
:
Suppressor of cytokine signaling 3 ( SOCS3 ), a negative
regulator of
leptin signaling, perhaps involves in cell survival and differentiation
Ernst et al., J Neurosci 2009
(Body Weight...) :
This unexpected finding coincides with POMC-cell-specific, Stat3 mediated upregulation of
SOCS3 expression
inhibiting both
leptin and insulin signaling as insulin stimulated PIP ( 3 ) ( phosphatidylinositol-3,4,5 triphosphate ) formation and protein kinase B ( AKT ) activation in POMC neurons as well as with the fact that insulin 's ability to hyperpolarize POMC neurons is largely reduced in POMC cells of Stat3-C ( POMC ) mice
You et al., Mol Cell Biol 2010
(Obesity) :
Importantly, both age dependent and diet induced deterioration of energy balance was paralleled with pronounced leptin resistance, which was largely attributable to attenuation of leptin-responsive hypothalamic STAT3 activation as well as prominently elevated expression of hypothalamic
SOCS3 , a key negative
regulator of
leptin signaling
Briancon et al., Diabetes 2010
(Insulin Resistance...) :
Suppressor of cytokine signaling
(SOCS)-3 and protein-tyrosine phosphatase 1B (PTP-1B) are two endogenous inhibitors of tyrosine kinase signaling pathways and
suppress both insulin and
leptin signaling via different molecular mechanisms
Alcazar et al., Endocrinology 2012
(Inflammation...) :
In addition,
SOCS-3 is
induced by both
leptin and inflammatory cytokines
Jorgensen et al., Diabetes 2013
(Insulin Resistance...) :
SOCS3 inhibits
leptin signaling in the hypothalamus and insulin signal transduction in adipose tissue and the liver
Jørgensen et al., J Exp Biol 2013
:
In an in vitro study with liver slices it was shown that recombinant rainbow trout
leptin stimulated SOCS1 and
SOCS3 expression, but not SOCS2, IGF-I or genes of enzymes involved in lipid ( G6PDH ) and amino acid ( AspAT ) metabolism