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EPHB2 — LPA
Text-mined interactions from Literome
Guo et al., J Urol 2000
(Prostatic Neoplasms) :
In the androgen-insensitive cell line, PC-3, EGF- and
LPA induced
ERK phosphorylation and cell proliferation ... Inhibition of EGF- and
LPA- induced
ERK activation with the EGF receptor inhibitor, AG1478, or the MEK inhibitor, PD98059, attenuated their proliferative effects
Xu et al., Biochem Pharmacol 2000
:
The
activation of
ERK1 and ERK2 by
LPA was PKC- and phosphatidylinositol 3-kinase ( PI 3-kinase ) -dependent
Leopoldt et al., J Cell Physiol 2000
:
Stimulation of these cells with bombesin,
lysophosphatidic acid (LPA) , endothelin, and platelet derived growth factor ( PDGF )
led to a marked increase in the tyrosine phosphorylation of these focal adhesion proteins and in
ERK activation
Cunnick et al., J Biol Chem 2000
:
Expression of Gab1DeltaPI3K had no apparent effect on
ERK2 activation by
LPA and EGF in the cells that we have examined ... These results establish a role for Gab1 in the LPA induced MAP kinase pathway and clearly demonstrate that Gab1-SHP2 interaction is essential for
ERK2 activation by
LPA and EGF
Caverzasio et al., J Bone Miner Res 2000
:
In contrast to their implication in epidermal growth factor (EGF) receptor tyrosine kinase signaling, the adaptor protein Shc, the Grb2/Sos complex, and the small G protein Ras were not involved in the activation of
Erk induced by either
LPA or PGF2alpha in MC3T3-E1 cells, suggesting that activation of Erk by Gi and Gq protein coupled receptors is Ras independent in these cells
Hong et al., Biochem Biophys Res Commun 2001
:
Moreover, accumulation of phosphatidic acid ( PA ), a product of PLD action, potentiated the
LPA induced
ERK activation in GP-PLD1 cells while blocking of PA production with the treatment of 1-butanol attenuated LPA induced ERK phosphorylation ... From these results, we suggest that
LPA activate PLD1 through pertussis toxin-sensitive G protein and PKC dependent pathways, then PA produced from PLD1 activation facilitate
ERK phosphorylation
Sautin et al., Am J Physiol Cell Physiol 2001
:
In C. difficile toxin treated cells,
LPA induced phosphorylation of
Erk1/Erk2 was rapid but transient, while p90RSK and Elk-1 phosphorylation did not change significantly
Schmitz et al., Biochem Biophys Res Commun 2002
:
Src dependent transactivation of receptor tyrosine kinases has been previously demonstrated to mediate
LPA induced activation of MAP kinase
ERK1/2
Wu et al., Biochim Biophys Acta 2002
:
In the last several years, the epidermal growth factor (EGF) receptor has been recognized as a protein tyrosine kinase that plays a central role in mediating
LPA induced tyrosine phosphorylation and
Erk MAP kinase activation
Daaka et al., Biochim Biophys Acta 2002
(MAP Kinase Signaling System) :
Induction of
ERK by
LPA proceeds via Gbetagamma dependent activation of tyrosine kinases, including the epidermal growth factor (EGF) receptor and c-Src ... Further,
LPA induced
ERK activation involves matrix metalloproteinases ( MMPs ), which cause the release of active EGFR ligands
Kue et al., Int J Cancer 2002
(MAP Kinase Signaling System...) :
Accordingly, we show that inhibition of EGFR kinase activity attenuates the
LPA regulated
ERK activation ... In addition, we find that the
LPA regulated tyrosine phosphorylation of EGFR and activation of
ERK are attenuated by batimastat, a generic inhibitor of matrix metalloproteinases ( MMP )
Budnik et al., Mol Endocrinol 2003
:
This functional inhibition of either Gi or Ras failed, however, to affect the
LPA induced
ERK-phosphorylation ... Surprisingly, functional inhibition of Rho-GTPase, in C3-exotoxin lipofected cells, markedly reduced
LPA stimulated phosphorylation of
ERK , without affecting the EGF induced stimulation of MAPK ... The findings indicate that
LPA transiently
stimulates MAPK
ERK in LPA1/edg2 expressing theca cells and suggest an alternative mechanism regulating the activation of ERK that differs from the canonical EGF-Ras-MAPK kinase pathway
Ediger et al., Eur Respir J 2003
(Cell Transformation, Neoplastic...) :
LPA and EGF both
activated ERK but had no synergistic effect when combined
Robinson-White et al., Hum Mol Genet 2003
:
There was a greater rate of growth in mutant cells ; forskolin and isoproterenol inhibited
LPA induced
ERK1/2 phosphorylation in normal but not in mutant cells ... We conclude that PKA activity in CNC cells is increased and that its stimulation by forskolin or isoproterenol increases
LPA induced
ERK1/2 phosphorylation, cell metabolism and proliferation
Wang et al., J Biol Chem 2003
:
In primary cultures of human bronchial epithelial cells ( HBEpCs ),
LPA stimulated tyrosine phosphorylation of PDGF-R beta and threonine/tyrosine phosphorylation of
ERK1/2
Stähle et al., J Cell Sci 2003
(Neoplasm Metastasis...) :
LPA induced ERK activation results in a transient translocation of the phosphorylated
ERK to newly forming focal contact sites at the leading edge of the migrating cells
Oh et al., Mol Cell Biol 2004
:
In addition, NHERF2 increases
LPA induced
ERK activation, which is followed by cyclooxygenase-2 induction via a PLC dependent pathway
Deng et al., J Biol Chem 2004
:
In EGFR ( Y5F ) -expressing cells,
LPA failed to elicit tyrosine phosphorylation of Src homologous and collagen protein ( SHC ) and
caused only a modest increase in
ERK1/2 phosphorylation similar to that in wild-type B82L cells ... The present data pinpoint the lack of importance of the intrinsic kinase activity in contrast to the importance of autophosphorylation sites of the EGFR for SHC phosphorylation in the enhancement of select
ERK1/2 dependent
LPA responses
Wallert et al., Cell Signal 2005
:
Activation of
ERK by phenylephrine and
LPA occurs in a dose- and time dependent manner ... To further demonstrate the specificity of the phenylephrine and
LPA regulation of NHE1 and
ERK , CCL39 cells were transfected with a kinase inactive MEK ... The data indicate that ERK activation is essential for phenylephrine stimulation of NHE1, and that
ERK and RhoA are
involved in
LPA stimulation of NHE1 by more than one mechanism ... These studies indicate a direct involvement of ERK in the alpha ( 1 ) -adrenergic activation of NHE1 and a significant
role for both
ERK and RhoA in
LPA stimulation of NHE1 in CCL39 fibroblasts
Shah et al., Mol Endocrinol 2005
:
Overexpression of dominant negative mutants of Ras or EGF-R, and selective inhibition of EGF-R kinase with AG1478, significantly reduced
LPA induced
ERK1/2 phosphorylation ...
LPA induced
ERK1/2 activation occurs predominantly through EGF-R transactivation by Gi/Src and partly through activation of protein kinase C, which acts downstream of EGF-R and Ras ... In contrast,
LPA induced phosphorylation of Shc and
ERK1/2 in clonal hepatocytes ( C9 cells ) was primarily mediated through MMP dependent transactivation of the EGF-R
Bektas et al., J Cell Biol 2005
(Carcinoma...) :
Conversely, down regulating expression of endogenous AGK inhibited EGF- but not
LPA induced
ERK1/2 activation and progression through the S phase of the cell cycle
Lai et al., Mol Cell Biol 2005
:
However, it abolishes the association of TRIP6 with Crk and p130cas in cells and significantly reduces the function of TRIP6 to promote
LPA induced
ERK activation
Gesty-Palmer et al., J Biol Chem 2005
:
In cells lacking beta-arrestin 2, > 80 % of
LPA stimulated
ERK1/2 phosphorylation was mediated by transactivated EGF receptors
Cechin et al., Neurochem Res 2005
(Glioma) :
Inhibition of Rho kinase or NHE1 did not reduce the
LPA induced phosphorylation of
ERK , Akt or CREB
Kim et al., Biochem Pharmacol 2005
:
Pertussis toxin almost completely inhibited the
LPA induced cellular proliferation and
ERK activation, indicating the role of G ( i/o ) protein ( s ) in the processes
Spiegel et al., Biochem Soc Trans 2005
(Prostatic Neoplasms) :
Intriguingly, down-regulation of endogenous AGK inhibited EGF ( epidermal growth factor ), but not
LPA induced
ERK1/2 ( extracellular-signal regulated kinase 1/2 ) activation and progression through the S-phase of the cell cycle
Kim et al., Cell Signal 2006
:
GqI expression also attenuated
LPA induced
ERK1/2 and Akt activation by 40-50 % ... Furthermore,
ERK activation in
response to
LPA was also attenuated in VSMCs with Adv-GqI
Müller et al., Endocrinology 2006
(Leydig Cell Tumor) :
LPA , but not ANP,
enhances ERK phosphorylation and induces cell rounding together with a dramatic reorganization of actin filaments
Zhang et al., Am J Physiol Cell Physiol 2006
:
Pertussis toxin ( PTX ) blocks LPA induced activation of p38 and
ERK but only slightly
inhibits LPA induced activation of Akt ...
LPA induced
activations of p38,
ERK , and Akt kinases, as well as proliferation, are inhibited by Ki16425
Zhang et al., Cell Signal 2007
:
MAGI-3 regulates
LPA induced
activation of
Erk and RhoA ... Overexpression of MAGI-3 in SW480 cells showed no apparent effect on
LPA induced activation of
Erk and Akt ... In contrast, silencing of MAGI-3 expression by siRNA drastically inhibited
LPA induced
Erk activation, suggesting that the lack of an effect by overexpression was due to the high endogenous MAGI-3 level in these cells
Pilquil et al., J Biol Chem 2006
:
These included decreased
LPA induced activation of
ERK and Rho, and the basal activities of Rac and Cdc42
Pazos et al., FEBS J 2007
(Adenocarcinoma...) :
Furthermore,
LPA induced
ERK activation was found to be independent of matrix metalloproteinases ; thus, c-Src acted as the scaffold transactivating epidermal growth factor receptor
Obara et al., Cell Signal 2008
:
In addition,
lysophosphatidic acid (LPA) attenuated the EGF induced
ERK5 phosphorylation in LPA ( 1 ) receptor- and G ( i/o ) -dependent manners ... On the other hand,
LPA alone
activated ERK1/2 via Gbetagamma subunits and Ras and potentiated EGF induced ERK1/2 phosphorylation at late time points ...
LPA did not affect cAMP levels after EGF treatment, and the reagents promoting cAMP production such as forskolin and cholera toxin also
attenuated the EGF induced
ERK5 phosphorylation, indicating that the inhibitory effect of LPA on ERK5 inhibition via G ( i/o ) is not due to inhibition of adenylyl cyclase by Galpha ( i/o ) ... However, the inhibitory
effect of
LPA on
ERK5 was abolished in PC12 cells stably overexpressing C-terminus of GPCR kinase2 ( GRK2 ), and overexpression of Gbeta ( 1 ) and gamma ( 2 ) subunits also suppressed ERK5 phosphorylation by EGF ... These results strongly suggest that
LPA negatively
regulates the EGF induced
ERK5 phosphorylation through Gbetagamma subunits
Yin et al., Invest Ophthalmol Vis Sci 2009
:
Early, but not late,
ERK1/2 phosphorylation in
response to wounding,
LPA , and ATP was EGFR independent, but sensitive to the inhibitors of calcium influx, protein kinase C and Src kinase
Taghavi et al., Oncogene 2008
(Cell Transformation, Neoplastic...) :
The transforming ability of LPA1, LPA2 and LPA4 was confirmed by tumor formation assays in vivo and correlated with prolonged
ERK1/2 activation in
response to
LPA
Liszewska et al., Endocrinology 2009
:
LPA activated phosphorylation of the MAPK
ERK1/2 in ovine trophectoderm derived cells
Kim et al., Arch Pharm Res 2008
:
Of the three major MAPKs, only
ERK1/2 was
activated by
LPA in a time dependent manner
Hurst et al., BMC neuroscience 2008
:
LPA and S1P also
induce p44/42
ERK MAP kinase phosphorylation in these cells and stimulate cell proliferation via G i/o coupled receptors in an Epidermal Growth Factor Receptor (EGFR)- and ERK dependent pathway
Jeong et al., Exp Mol Med 2008
(Ovarian Neoplasms) :
Higher expression of LPA2 mRNA was observed in CAOV-3 cells, and transfection of the cells with a selective LPA2 siRNA significantly inhibited
LPA induced
activation of EGFR and
ERK , as well as COX-2 expression
Karagiosis et al., J Cell Physiol 2009
:
While LPA exposure transactivates the EGF receptor in many cell types,
LPA stimulated
ERK1/2 activation in MC3T3-E1 cells was unaffected by the inhibition of EGF receptor function
Ambesi et al., Mol Cancer Res 2009
:
Both
LPA and S1P
activated PI3K,
Ras/ERK , and Rho/Rho kinase pathways, leading to migration, G ( 1 ) -S cell cycle progression, and stress fiber formation, respectively ... Although
LPA and S1P
activated both PI3K/Akt and
Ras/ERK signaling through G ( i ), anastellin inhibited only the Ras/ERK pathway
Stoll et al., J Invest Dermatol 2010
:
Lysophosphatidic acid (LPA) induced
ERK phosphorylation was also strongly EGFR and MP dependent and markedly inhibited by neutralization of HB-EGF
George et al., J Periodontol 2009
(Calcium Signaling) :
LPA stimulated
ERK1/2 phosphorylation via LPA ( 1 ) ( -3 )
Saunders et al., Free Radic Biol Med 2010
(Ovarian Neoplasms) :
Exogenous
LPA further
stimulated ERK and Akt phosphorylation and NF-?B activity
Costello et al., International journal of molecular sciences 2011
:
Both S1P and
LPA induced ERK phosphorylation and
ERK- and G ( i ) -dependent up-regulation of ICAM-1 expression, with differing time courses ...
LPA also
induced ERK- and G ( i ) -dependent up-regulation of the eosinophil chemoattractant, CCL-26 ... The eosinophil granule protein eosinophil peroxidase (EPO) induced
ERK dependent up-regulation of transcription of S1P(1),
LPA ( 1 ), LPA ( 2 ) and LPA ( 3 ), providing the situation whereby eosinophil granule proteins may enhance S1P- and/or LPA- induced eosinophil accumulation at nerve cells in allergic conditions
Wu et al., Mol Cancer Res 2011
(Breast Neoplasms...) :
LPA stimulated p21 via LPA ( 1 ) and
LPA ( 2 ) receptors and
Erk dependent
activation of the CCAAT/enhancer binding protein beta transcription factor independent of p53
Ward et al., Oncogene 2013
(Disease Models, Animal...) :
In addition, tumor cell cultures derived from CD97 transgenic as compared with non-transgenic mice demonstrated enhanced, constitutive and
LPA stimulated
ERK activation
Violet et al., Biochim Biophys Acta 2012
:
In this study we show that DGPP 8 : 0 does not antagonize
LPA dependent activation of
ERK ( 1/2 ) MAP kinases but strongly stimulated them in various mammalian cell lines
Cook et al., EMBO J 1993
:
RapV12 antagonizes Ras dependent
activation of ERK1 and
ERK2 by
LPA and EGF in Rat-1 fibroblasts
Cook et al., Biochem J 1996
:
The EC50 for
LPA stimulated
ERK activation after 10 min, the time of peak response, was 2 orders of magnitude to the left of that for the sustained response after 3 h or that for DNA synthesis after 22 h, with the result that non-mitogenic doses stimulated a maximal peak response but no second phase ... Activation of protein kinase C and Ca2+ fluxes played a minor and transient role in
regulation of
ERK1 activity by
LPA in Rat-1 cells
Cadwallader et al., Biochem J 1997
:
The
activation of
ERK1 by
lysophosphatidic acid (LPA) and endothelin 1 (Et-1) was compared in Rat-1 cells
Cook et al., J Biol Chem 1997
:
Inhibition of
LPA stimulated MEK and
ERK activation with PD98059 and pertussis toxin, a selective inhibitor of Gi-protein coupled signaling pathways, reduced LPA stimulated MKP-1 expression by only 50 %, suggesting the presence of additional MEK- and ERK independent pathways for MKP-1 expression
Sasaki et al., J Biochem 1998
:
These results indicate that the signal transduction pathways of
LPA induced JNK and
ERK activations are distinct ... Thus, this is the first report showing that
LPA induces not only
ERK activation but also JNK activation, which may be responsible for the induction of DNA synthesis in LPA stimulated Swiss 3T3 fibroblasts