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EPHB2 — RAC1
Pathways - manually collected, often from reviews:
-
NCI Pathway Database EPHB forward signaling:
RAC1/GDP complex (RAC1)
→
Ephrin B1/EPHB1-2 complex (EFNB1-EPHB1_EPHB2)
(modification, collaborate)
Batlle et al., Cell 2002*
Evidence: assay
-
NCI Pathway Database Ephrin B reverse signaling:
Ephrin B1/EPHB1-2/Tiam1 complex (EFNB1-EPHB1_EPHB2-TIAM1)
→
RAC1/GDP complex (RAC1)
(modification, activates)
Tanaka et al., EMBO J 2004
Evidence: mutant phenotype, assay
-
NCI Pathway Database Ephrin B reverse signaling:
Ephrin B1/EPHB1-2/Tiam1 complex (EFNB1-EPHB1_EPHB2-TIAM1)
→
RAC1/GTP complex (RAC1)
(modification, activates)
Tanaka et al., EMBO J 2004
Evidence: mutant phenotype, assay
-
Reactome Reaction:
EPHB2
→
RAC1
(indirect_complex)
Zhang et al., J Cell Biol 2003, Marston et al., Nat Cell Biol 2003
-
Reactome Reaction:
EPHB2
→
RAC1
(reaction)
Penzes et al., Neuron 2003, Bokoch et al., Annu Rev Biochem 2003, Zhang et al., J Cell Biol 2003, Marston et al., Nat Cell Biol 2003, Tolias et al., Neuron 2005, Zhang et al., J Neurosci 2005
Text-mined interactions from Literome
Clerk et al., Mol Cell Biol 2001
(Cardiomegaly) :
In transfection experiments, dominant negative
N17Rac1 inhibited activation of
ERK by endothelin 1, whereas activated V12Rac1 cooperated with c-Raf to activate ERK
Nosaka et al., Biochem Biophys Res Commun 2001
(Fibrosarcoma) :
Rac is activated by tumor necrosis factor alpha and is
involved in activation of
Erk
Woo et al., J Biol Chem 2002
:
Consistent with those findings, leukotriene B ( 4 )
Rac-dependently stimulates ERK and cytosolic phospholipase A ( 2 ) activity, and transient transfection with plasmid expressing Rac ( V12 ), a constitutively activated Rac1 mutant, also dose-dependently
stimulates ERK activity
Arai et al., Oncogene 2002
:
A dominant negative
Rac mutant, Rac17N, also
inhibited the cytokine induced activation of
Erk as well as Elk-1
Woo et al., Mol Cells 2002
(MAP Kinase Signaling System) :
Our results showed that LPS induced the activation of
ERK and p38 MAP kinase in a
Rac dependent manner, suggesting a mediatory role of Rac1 in LPS signaling to MAPKs stimulation
Eblen et al., Mol Cell Biol 2002
(MAP Kinase Signaling System) :
Phosphorylation of
ERK2-delta19-25 but not of wild-type ERK2 in response to Ras V12 was greatly
inhibited by dominant negative
Rac ... Activated forms of
Rac and Cdc42 could
enhance the association of wild-type
ERK2 with MEK1 but not with MEK2 in serum starved adherent cells
Rul et al., Ann N Y Acad Sci 2002
(MAP Kinase Signaling System) :
Here, we describe that the inhibition of
Rac1 or Cdc42 signaling
leads to MAPK
ERK activation via a pathway involving PI(3)K, Akt, Raf, and MEK, but not Ras
Zhong et al., Blood 2003
(MAP Kinase Signaling System) :
Rac and Cdc42, but not Ras or Rho, were
responsible for this
MAPK/ERK activation ... PAK1 ( p21 activated kinase 1 ) activation is induced by C albicans, suggesting that PAK1 may also be involved in the
Rac1 activation of
MAPK/ERK ... We conclude from these data that
Rac/Cdc42 dependent
activation of
MAPK/ERK is a critical event in the immediate phagocytic response of PMNs to microbial challenge
Penzes et al., Neuron 2003
:
Activation of the
EphB receptor
induces translocation of the Rho-GEF kalirin to synapses and activation of
Rac1 and its effector PAK
Vial et al., Cancer Cell 2003
(Colonic Neoplasms...) :
ERK-MAPK signaling coordinately
regulates activity of
Rac1 and RhoA for tumor cell motility
Shin et al., J Biol Chem 2004
:
Inhibition of
ERK or PAK2, the kinases upstream of p85 betaPIX in the bFGF signaling,
prevents Rac1 activation, suggesting that phosphorylation of p85 betaPIX functions upstream of Rac1 activation
Hammarberg et al., Biochem Pharmacol 2004
:
In addition, inhibition of
Rac/Cdc42 , small GTPases of the Rho family, by clostridium toxin B, diminished p38 phosphorylation but did not
affect ERK1/2
Tanaka et al., EMBO J 2004
:
In cells coexpressing Tiam1 and ephrin-B1,
Rac1 is
activated by the extracellular stimulation of clustered soluble
EphB2 receptors
Eblen et al., Mol Cell Biol 2004
(MAP Kinase Signaling System) :
It was previously shown that
Rac-p21 activated kinase (PAK) signaling
regulated the physical association of MEK1 with
ERK2 through phosphorylation sites in the proline-rich sequence (PRS) of MEK1
Gorin et al., Biochem J 2004
(Hypertrophy...) :
Moreover, dominant negative
Rac1 ( N17Rac1 )
blocks activation of
ERK1/ERK2 in response to Ang II and AA, whereas constitutively active Rac1 resulted in an increase in ERK1/ERK2 activity
Maeda et al., Biochem Biophys Res Commun 2004
:
Expression of Gab1 PI3K-m in SK-N-MC human primitive neuroectodermal tumor cells expressing wild-type RET markedly impaired Akt phosphorylation,
Rac1 activation, and lamellipodia formation that were
induced by GDNF whereas expression of Gab1 SHP2-m partially impaired
Erk activation
Nishida et al., J Biol Chem 2005
:
Dominant negative
Rac inhibited angiotensin II-stimulated ROS production, JNK activation, and p38 MAPK activation but did not
affect ERK activation
Qu et al., J Biochem 2005
(Diabetes Mellitus, Experimental...) :
FcepsilonRI mediated tyrosine phosphorylation of Syk, Gab2, and phospholipase C-gamma1, and
activation of c-Jun N-terminal kinase (JNK), extracellular signal regulated kinase (
ERK ), p38 mitogen activated protein kinase ( MAP kinase ), and inhibitor of nuclear factor kappaB kinase ( IKK ), and generation of
Rac1 are unaffected in cells overexpressing the truncated Cbl-b in the lipid raft
Jin et al., Am J Physiol Gastrointest Liver Physiol 2006
(MAP Kinase Signaling System) :
However, inhibition of
Rac1 significantly decreased apoptosis in the
presence of
ERK1/2 and Akt inhibitors, similar to the effect observed with NSC-23766 alone in response to TNF-alpha
Chaturvedi et al., J Biol Chem 2007
:
We investigated whether Src and
Rac1 mediate deformation
induced FAK and
ERK phosphorylation and proliferation in human Caco-2 and rat IEC-6 intestinal epithelial cells
Slupsky et al., Am J Pathol 2007
(Leukemia, Hairy Cell) :
Inhibition with toxin B showed that
Rac1 plays no role in
ERK activation in HCs
Tushir et al., EMBO J 2007
:
Second, ARF6 induced
ERK activation
regulates Rac1 activation during tubule initiation through the expression of the receptor for urokinase type plasminogen activator
Bruinsma et al., Proc Natl Acad Sci U S A 2007
(MAP Kinase Signaling System) :
Chimaerin and
Rac regulate cell number, adherens junctions, and
ERK MAP kinase signaling in the Drosophila eye
Wu et al., J Biol Chem 2007
(MAP Kinase Signaling System) :
Instead, knock down of the novel oxidase Nox4 completely suppressed Tat dependent Ras and
ERK activation downstream of
Rac1 and RhoA
Tan et al., Biochim Biophys Acta 2008
(Carcinoma, Hepatocellular...) :
The
Rac1 activation by HBV replication also
resulted in the phosphorylation of
ERK1/2 and AKT, the downstream targets of Rac1 signaling cascade
Notcovich et al., Exp Cell Res 2010
:
On the other hand, H1R induced ERK1/2 activation was inhibited by U73122 but not affected by C3 or beta2-chimaerin, suggesting that
ERK1/2 activation was dependent on PLC and
independent of RhoA or
Rac
Kowluru et al., Diabetes 2010
:
Lastly, siRNA mediated silencing of endogenous expression of
ERK1/2 markedly
attenuated glucose induced
Rac1 activation and insulin secretion
Yuan et al., Clin Exp Metastasis 2010
(Brain Neoplasms...) :
In this study, we investigated whether
ERK regulates
Rac1/Pak1 signaling and is critically linked to MB cell migration ... We conclude that
Rac1/Pak1 signaling is critical to MB cell migration and is functionally
dependent on
PDGFRß/ERK activity
Déléris et al., J Biol Chem 2011
(MAP Kinase Signaling System) :
We show that group I PAKs phosphorylate ERK3 and
ERK4 on Ser-189 and Ser-186, respectively, both in vitro and in vivo, and that expression of activated
Rac1 augments this response ... Reciprocally, silencing of PAK1/2/3 expression by RNA interference ( RNAi ) completely abolishes
Rac1 induced Ser-189 phosphorylation of
ERK3
Du et al., PloS one 2011
(Breast Neoplasms) :
PI3K and
ERK induced
Rac1 activation mediates hypoxia induced HIF-1a expression in MCF-7 breast cancer cells ... Taken together, our study demonstrated that hypoxia induced HIF-1a expression involves a cascade of signaling events including ROS generation,
activation of PI3K and
ERK signaling, and subsequent activation of
Rac1
Curtis et al., Mol Cell Neurosci 2012
(MAP Kinase Signaling System) :
Rac1b regulates NT3 stimulated
Mek-Erk signaling, directing marrow isolated adult multilineage inducible ( MIAMI ) cells toward an early neuronal phenotype
Yan et al., Breast Cancer Res 2012
(Breast Neoplasms) :
With Rac1-specific inhibitor, dominant negative mutant Rac1 ( N17Rac1 ) and specific small interfering RNA, the
effect of
Rac1 on IR-induced G2/M checkpoint response and
ERK1/2 activation was examined in human breast cancer cells
Eastman et al., Cell Signal 2012
:
Autonomous
ERK activation by uPAR
requires H-Ras and
Rac1
Hu et al., Cell Signal 2013
(Carcinoma, Hepatocellular...) :
Inhibitor studies revealed that ERK was required for HGF induced paxillin phosphorylation at Ser178, whereas PKC and
Rac-1 may
suppress HGF induced phosphorylation of
ERK and paxillin ( at Ser178 ) and upregulate phosphorylation of paxillin at Tyr31
Frost et al., Mol Cell Biol 1996
:
Although neither activated
Rac nor the PAKs
stimulate ERK2 activity, overexpression of either dominant negative Rac2 or the N-terminal regulatory domain of PAK1 inhibits Ras mediated activation of ERK2, suggesting a permissive role for Rac in the control of the ERK pathway
Zohn et al., Mol Cell Biol 1998
(Cell Transformation, Neoplastic) :
Fourth, Mas and
Rac1 strongly
activated the JNK and p38, but not
ERK , mitogen activated protein kinases
Miranti et al., Curr Biol 1998
:
This pathway may regulate multiple downstream events in hematopoietic cells, including
Rac induced lamellipodia formation, tyrosine phosphorylation of Cbl, and activation of JNK,
ERK2 and the phosphatidylinositol 3'-kinase regulated kinase Akt