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IRS1 — LEP
Pathways - manually collected, often from reviews:
-
Reactome Reaction:
IRS1
→
LEP
(indirect_complex)
Szanto et al., Proc Natl Acad Sci U S A 2000, Martín-Romero et al., Cell Immunol 2001, Duan et al., J Biol Chem 2004, Li et al., Mol Endocrinol 2007, Hill et al., J Clin Invest 2008, Buettner et al., Nat Med 2008, Bjørbaek et al., J Biol Chem 1997
-
Reactome Reaction:
IRS1
→
LEP
(reaction)
Duan et al., J Biol Chem 2004, Li et al., Mol Endocrinol 2007
Text-mined interactions from Literome
Szanto et al., Proc Natl Acad Sci U S A 2000
:
In Fao cells,
leptin alone had no effects on the insulin signaling pathway, but leptin pretreatment transiently
enhanced insulin induced tyrosine phosphorylation and PI 3-kinase binding to
IRS-1 , while producing an inhibition of tyrosine phosphorylation and PI 3-kinase binding to IRS-2
Bifulco et al., Placenta 2003
(Choriocarcinoma...) :
HG culturing also enhanced
leptin stimulated
insulin receptor substrate 1 (IRS1) and MAPK phosphorylation
Carvalheira et al., Biol Chem 2003
:
This phenomenon parallels the
leptin induced tyrosine phosphorylation of STAT3, STAT5b,
IRS-1 and IRS-2
Duan et al., J Biol Chem 2004
:
SH2-B promotes
insulin receptor substrate 1 (IRS1)- and IRS2 mediated activation of the phosphatidylinositol 3-kinase pathway in
response to
leptin ... Here we report that SH2-B, a JAK2 interacting protein, promotes activation of the PI 3-kinase pathway by recruiting
insulin receptor substrate 1 (IRS1) and IRS2 in
response to
leptin ... Consequently, SH2-B dramatically enhanced
leptin stimulated tyrosine phosphorylation of
IRS1 and IRS2 in HEK293 cells stably expressing LRb, thus promoting association of IRS1 and IRS2 with the p85 regulatory subunit of PI 3-kinase and phosphorylation and activation of Akt ... SH2-B mutants with lower affinity for IRS1 and IRS2 exhibited reduced ability to promote association of JAK2 with IRS1, tyrosine phosphorylation of IRS1, and association of
IRS1 with p85 in
response to
leptin ... Moreover, deletion of the SH2-B gene impaired
leptin stimulated tyrosine phosphorylation of endogenous
IRS1 in mouse embryonic fibroblasts (MEF), which was reversed by reintroduction of SH2-B
Benomar et al., Biochem J 2005
:
Furthermore,
leptin or insulin pre-treatment
increased basal PI3K activity and
IRS-1 or IRS-2 association with p85 and abolished acute insulin or leptin effect, in addition to the down-regulation of IRS-1 and IRS-2
Hennige et al., FASEB J 2006
(Obesity) :
Here we show in various cell models that the adipose hormone
leptin , a putative mediator in obesity related insulin resistance,
promotes phosphorylation of Ser-318 in
Irs1 by a janus kinase 2, Irs2, and PKC dependent pathway
Li et al., Mol Endocrinol 2007
:
JAK2 was required for
leptin stimulated phosphorylation of
insulin receptor substrate 1 (IRS1) , an upstream activator of the phosphatidylinositol 3-kinase pathway
Fang et al., Diabetologia 2009
:
Adiponectin can also enhance insulin sensitivity via direct signalling crosstalk ; here we show that enhanced insulin stimulated
IRS-1 ( Y612 ) and Akt ( T308 ) phosphorylation in response to fAd was
attenuated by
leptin
Bełtowski et al., Life Sci 2009
(Disease Models, Animal...) :
Leptin increased tyrosine phosphorylation of
insulin receptor substrate-1 (IRS-1) in the aortic wall, and this effect was impaired in obese and fructose fed animals
Mehebik-Mojaat et al., J Cell Biochem 2009
(Insulin Resistance) :
In the
presence of
leptin and insulin, ( i )
IRS-1 was phosphorylated on Ser ( 307 ) and this effect was prevented by PKA inhibitors, ( ii ) JAK-2 was dephosphorylated, an effect prevented by SHP-1 inhibitor
Moon et al., Diabetologia 2012
:
Leptin , but not amylin,
increased IRS-1 phosphorylation in GT1-7 hypothalamic, but not in C2C12 muscle and AML12 liver cell lines
Tsuchiya et al., Yakugaku Zasshi 2012
(Disease Progression...) :
In in vitro experiments, ATRA significantly enhanced insulin induced
IRS1 tyrosine phosphorylation solely in the
presence of
leptin
Nazarians-Armavil et al., Mol Endocrinol 2013
:
Neuronal insulin resistance, as assessed by attenuated Akt phosphorylation, blocked
leptin mediated signal transduction and agouti related peptide, urocortin-2,
IRS1 , IRS2, and insulin receptor synthesis