◀ Back to MAPK3
MAPK3 — TGFB1
Pathways - manually collected, often from reviews:
-
OpenBEL Selventa BEL large corpus:
MAPK3
→
TGFB1
(increases, TGFB1 Activity)
Evidence: TGF-b was also shown to induce Egr-1 expression in normal dermal fibroblasts [32]. The response was rapid and transient, occurred via an ERK1/2- dependent and Smad-independent mechanism, and involved transcriptional stimulation.
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OpenBEL Selventa BEL large corpus:
MAPK3
→
TGFB1
(increases, TGFB1 Activity)
Caraci et al., Pharmacol Res 2008*
Evidence: TGF-beta1 treatment activated the MAPK pathway, as shown by an increased phosphorylation of extracellular-regulated kinases (ERK)1/2 after 30 min of exposure.
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NCI Pathway Database ALK1 signaling events:
Erk1-2 (MAPK3/MAPK1)
→
TGFB1 (dimer) complex (TGFB1)
(modification, collaborate)
Lee et al., J Biol Chem 2007
Evidence: mutant phenotype, assay
Text-mined interactions from Literome
Yamamoto et al., Eur J Biochem 1999
:
The rapid
activation of
p42/44 MAP kinase (MAPK) by
TGF-beta1 was eliminated completely, and transcriptional activation by TGF-beta1 of the plasminogen activator inhibitor-1 gene was reduced by 50 % in both endothelial cells and Mv1Lu when they were infected with AdCARasY57
Wenner et al., Braz J Med Biol Res 1999
(Cell Transformation, Neoplastic) :
TGF-beta 1 delayed EGF- or PDGF induced cyclin D1 expression and
blocked the induction of active
p42/p44MAPK ... The mechanism by which
TGF-beta 1 induces a block in
p42/p44MAPK activation is being examined and the possibility that TGF-beta 1 regulates phosphatase activity is being tested
Han et al., J Biol Chem 2000
:
TGF-beta1/TGF-beta2 increased phosphorylation of both
mitogen activated protein ( MAP ) kinase and PPAR-gamma, whereas MAP kinase inhibitors reversed suppression of CD36 and inhibited PPAR-gamma phosphorylation induced by TGF-beta1/TGF-beta2
Johansson et al., J Cell Sci 2000
(Carcinoma, Squamous Cell) :
In addition,
transforming growth factor- ( beta ) ( TGF- ( beta )
activated p38
MAPK in both cell lines, and ERK2 in A-5 cells
Kucich et al., Arch Biochem Biophys 2000
:
TGF-beta1 stimulation of fibronectin transcription in cultured human lung fibroblasts
requires active geranylgeranyl transferase I, phosphatidylcholine-specific phospholipase C, protein kinase C-delta, and p38, but not
erk1/erk2
Gruden et al., Diabetes 2000
:
Mechanical stretch induced fibronectin and
transforming growth factor-beta1 production in human mesangial cells is p38
mitogen activated protein kinase dependent
Junn et al., J Immunol 2000
:
In addition,
TGF-beta1 or H2O2
increased MAPK activity which was reduced by EGTA and NAC, suggesting that MAPK is involved in TGF-beta1 induced IL-6 expression
Brunetti et al., Thromb Haemost 2000
:
In conclusion, we report for the first time that PMN apoptosis is potently inhibited by platelet released mediators, that TGF-beta1 mediates an important part of this effect, and that p38
MAPK is
involved in the
TGF-beta1 signaling leading to its anti-apoptotic effect
Chin et al., American journal of physiology. Renal physiology 2001
:
TGF-beta(1) rapidly
induced p38
MAPK phosphorylation in wild-type and empty vector ( pcDNA3 ) -transfected control mesangial cells ... Interestingly, transfection with dominant negative TbetaR-II ( M ) failed to block
TGF-beta(1) induced p38
MAPK phosphorylation
Hashimoto et al., Am J Respir Crit Care Med 2001
:
The results showed that : ( 1 )
TGF-beta1 caused the phenotypic modulation of HLF to myofibroblasts in a dose- and a time dependent manner ; ( 2 ) TGF-beta1 induced increases in c-Jun-NH2- terminal kinase (JNK), p38 MAPK, and extracellular signal regulated kinase ( Erk ) phosphorylation and activity ; ( 3 ) the inhibitors CEP-1347, SB 203580, and PD 98059
attenuated TGF-beta1 induced JNK, p38
MAPK , and Erk activity, respectively ; and ( 4 ) CEP-1347, but not SB 203580 or PD 98059, attenuated the TGF-beta1 induced phenotypic modulation of HLF to myofibroblasts in a dose dependent manner
Westermarck et al., Mol Cell Biol 2001
(MAP Kinase Signaling System) :
In contrast, activation of stress activated c-Jun N-terminal kinase and p38 pathways by expression of constitutively active mutants of Rac,
transforming growth factor beta activated kinase 1 ( TAK1 ),
MAPK kinase 3 ( MKK3 ) , or MKK6 or by treatment with arsenite or anisomycin did not alone markedly enhance MMP-1 promoter activity
Karsdal et al., J Biol Chem 2001
(Bone Resorption) :
TGF-beta1 also
triggered activation of
Erk1/2 and p38 mitogen activated protein ( MAP ) kinase
Bhowmick et al., J Biol Chem 2001
:
Integrin beta 1 signaling is necessary for
transforming growth factor-beta activation of
p38MAPK and epithelial plasticity
Baxter et al., J Cardiovasc Pharmacol 2001
(Myocardial Infarction...) :
Cardioprotective effects of
transforming growth factor-beta1 during early reoxygenation or reperfusion are
mediated by p42/p44
MAPK ...
TGF-beta1 activated p42/p44
MAPK transiently in normoxic myocytes
Goldberg et al., Am J Physiol Lung Cell Mol Physiol 2002
:
p38
MAPK activation by
TGF-beta1 increases MLC phosphorylation and endothelial monolayer permeability
Sato et al., J Invest Dermatol 2002
(Scleroderma, Systemic) :
Role of p38
MAPK in
transforming growth factor beta stimulation of collagen production by scleroderma and healthy dermal fibroblasts ... In conclusion, this study demonstrates a costimulatory
role for p38
MAPK in
transforming growth factor beta induction of the collagen type I gene
Zhu et al., J Neurosci 2002
(Infarction, Middle Cerebral Artery...) :
TGF-beta1 concentration- and time-dependently
activated Erk1/2 and Rsk1 accompanied by an increase in Bad phosphorylation
Weigert et al., Diabetologia 2002
(Hyperglycemia) :
Co-incubation with ang II and high glucose had no additive effect on
TGF-beta 1 promoter activity, protein binding to the AP-1 box B or
activation of p38
MAPK
Hyman et al., Surgery 2002
(MAP Kinase Signaling System) :
We hypothesized that
TGF-beta1 activates endothelial cell MAPKs and
induces apoptosis through p38 (
MAPK ) activation ...
TGF-beta1 induced p38 (
MAPK ), extracellular signal regulated kinase 1/2, and c-Jun N-terminal kinase 1/2 activation and increased apoptosis ...
TGF-beta1 induces endothelial cell apoptosis through p38 (
MAPK ) activation
Cao et al., Am J Physiol Gastrointest Liver Physiol 2002
:
TGF-beta1 or addition of H ( 2 ) O ( 2 ) to HSCs
activated p38
MAPK with a rise in procollagen mRNA level ; these changes were blocked by catalase and SB-203580 and likewise by DLPC
Cao et al., Blood 2003
:
TGF-beta1 and ATRA
activate P42/44
mitogen activated protein ( MAP ) kinase with nearly identical kinetics, ruling out its involvement in these effects on Smad phosphorylation
Frippiat et al., Free Radic Biol Med 2002
:
Here we show that sustained p38 (
MAPK ) phosphorylation is
responsible for both H2O2 induced overexpression of
TGF-beta 1 and subsequent TGF-beta 1-induced appearance of these biomarkers
Fukuda et al., Virology 2002
(Cell Transformation, Neoplastic...) :
TGF-beta 1 activated
MAPK ( ERK 1/2 ) and p21 in the TGF-beta 1-susceptible cell line HSC-39 but not in GT38 cells
Selvamurugan et al., FEBS Lett 2002
(Breast Neoplasms...) :
These data indicate that
TGF-beta1 induced
MAPK and Smad pathways are involved in TGF-beta1 stimulated collagenase-3 expression in MDA-MB231 cells
Zhou et al., Zhonghua Yi Xue Za Zhi 2002
:
Furthermore, the functional and structural results showed that Ox-LDL regulates rat TGF-beta(1) gene expression through AP-1 binding site and c-Jun/AP-1 complex, it gives rise to the
involvement of protein kinase C, but not
p38MAPK , in Ox-LDL induced
TGF-beta(1) gene expression
Burt et al., Diabetologia 2003
:
Glucose induced
TGFbeta1 expression is
mediated by p38
mitogen-activated-protein-kinase ( p38-MAPK ) and this kinase is activated in the diabetic glomeruli ...
P38-MAPK inhibition using SB202190 ( 1 micro mol/l )
reduced hexosamine induced
TGFbeta1 expression in normal and high glucose
Mincione et al., Exp Cell Res 2003
:
These results were accompanied by
TGF-beta 1 inhibition of IGF-I stimulated
mitogen activated protein kinase phosphorylation and activation
Hubchak et al., J Am Soc Nephrol 2003
:
It also was determined that
TGF-beta1 activates ERK
mitogen activated protein kinase in mesangial cells to enhance Smad activation and collagen expression
Frank et al., J Biol Chem 2003
:
The inhibitory effect of
TGF-beta1 on sodium uptake and alphaENaC expression in ATII cells was
mediated by activation of the
MAPK , ERK1/2
Horowitz et al., J Biol Chem 2004
:
Activation of the pro-survival phosphatidylinositol 3-kinase/AKT pathway by
transforming growth factor-beta1 in mesenchymal cells is
mediated by p38
MAPK dependent induction of an autocrine growth factor
Lee et al., Int J Oncol 2004
(Stomach Neoplasms) :
Smad2 mediates
Erk1/2 activation by
TGF-beta1 in suspended, but not in adherent, gastric carcinoma cells ... Currently effects of cell adhesion status on the
TGF-beta1 mediated
Erk1/2 regulation and on its Smad- ( in ) dependency are not known ... In this study, we examined effects of cell adhesion status on the
TGF-beta1 mediated
Erk1/2 regulation, and roles of Smad proteins on the cell adhesion mediated effects, using a gastric carcinoma cell variant ... This
activation of
Erk1/2 by
TGF-beta1 in suspension was more enhanced by an overexpression of Smad2, but not of other Smads 2, 4, and 7, but abolished by a Smad2 reduction via an introduction of its siRNA
Kim et al., J Biol Chem 2004
(Carcinoma, Hepatocellular...) :
Although transforming growth factor beta1 ( TGF-beta1 ) acts via the Smad signaling pathway to initiate de novo gene transcription, the
TGF-beta1 induced
MAPK kinase activation that is involved in the regulation of apoptosis is less well understood
Falanga et al., Wound Repair Regen 2004
:
By Western blot analysis, Smad3 null mice fibroblasts showed a compensatory increase in
mitogen activated protein kinase phosphorylation in
response to
transforming growth factor-beta1 , suggesting that mitogen activated protein kinase overcompensation together with loss of Smad3 may be involved in the modulation of faster healing
Lechuga et al., Am J Physiol Gastrointest Liver Physiol 2004
:
Our results also show that this
TGF-beta1 mediated effect is de novo protein synthesis dependent and requires the activity of
p38MAPK , phosphatidylinositol 3-kinase, AKT, and p70 ( S6k )
Munshi et al., J Biol Chem 2004
(Carcinoma, Squamous Cell...) :
TGF-beta1 induced concomitant activation of ERK1/2 and p38
MAPK , and kinase inhibition studies revealed a negative regulatory role for ERK1/2 in modulating acquisition of MMP-2 activity
Suzuki et al., Clin Exp Nephrol 2004
:
Role of
mitogen activated protein kinase in the regulation of
transforming growth factor-beta induced fibronectin accumulation in cultured renal interstitial fibroblasts
Rhyu et al., J Am Soc Nephrol 2005
(Fibrosis...) :
Role of reactive oxygen species in
TGF-beta1 induced
mitogen activated protein kinase activation and epithelial-mesenchymal transition in renal tubular epithelial cells ... Because reactive oxygen species ( ROS ) are involved in TGF-beta1 signaling and are upstream signaling molecules to MAPK, this study examined the role of ROS in
TGF-beta1 induced
MAPK activation and EMT in rat proximal tubular epithelial cells ... Antioxidants effectively inhibited
TGF-beta1 induced cellular ROS, phosphorylation of Smad 2, p38
MAPK , and ERK, and EMT
Nakagawa et al., J Am Soc Nephrol 2005
:
In conclusion, TSP-1 expression is regulated by both ERK1/2 and p38
MAPK in rat proximal tubular cells and mouse fibroblasts in
response to
TGF-beta1
Kim et al., Invest Ophthalmol Vis Sci 2005
:
TGF-beta1 also
induced activation of Smad2, JNK1/2,
ERK1/2 , and p38 within 5 to 15 minutes, with peak activation at 15 to 60 minutes
Roux et al., J Biol Chem 2005
(Edema) :
The inhibitory effect of IL-1beta on alpha ENaC expression was mediated by the activation of p38
MAPK in both rat and human ATII cells and was
independent of the activation of alpha v beta6 integrin and
transforming growth factor-beta
Sohn et al., Kidney Int 2005
:
Inhibition of p38 ( mapk ) or
p42/44(mapk) activities did not
affect LDL induced
TGF-beta1 , CTGF, and collagen I expression, whereas inhibition of c-Jun NH2-terminal kinase (JNK) suppressed LDL induced TGF-beta, CTGF, and collagen I expression
Leung et al., Nephrol Dial Transplant 2005
:
The GDP induced VEGF and
transforming growth factor ( TGF ) -beta synthesis in HPMC was partially
reduced by either the p42/p44
MAPK inhibitor ( PD98059 ) or the PKC inhibitor ( staurosporine )
Han et al., J Clin Invest 2005
(Carcinoma in Situ...) :
However, Delta ( beta ) RII did not alter
TGF-beta1 mediated expression of RhoA/Rac and
MAPK , which contributed to increased metastasis
Leivonen et al., J Invest Dermatol 2005
:
Smad3 and
extracellular signal regulated kinase 1/2 coordinately
mediate transforming growth factor-beta induced expression of connective tissue growth factor in human fibroblasts
Fang et al., J Cell Biochem 2005
:
Nicotine treatment down-regulated
TGF-beta1 induced p38
MAPK phosphorylation
Deaton et al., J Biol Chem 2005
:
Finally, examination of MAPK signaling demonstrated that
TGF-beta1 increased the activity of p38
MAPK , which was required for activation of the SMC marker gene promoters
Inagaki et al., J Biol Chem 2005
:
Here, we show that 1 ) KTI suppressed
TGF-beta1 induced phosphorylation of Src,
ERK1/2 , and Akt by 40-60 % ; 2 ) KTI was insensitive to suppress the phosphorylation of ERK1/2 and Akt in the constitutively active ( CA ) -c-Src ( Y529F ) cells ; 3 ) uPA expression was up-regulated in TGF-beta1 stimulated HRA cells and in unstimulated Y529F cells ; 4 ) the addition of KTI reduced the TGF-beta1 induced increase of uPA gene and protein expression in the wild-type c-Src transfected cells ( in contrast, KTI could not inhibit uPA expression in the Y529F cells ) ; and 5 ) CA-c-Src transfection resulted in a 2-fold increase in invasiveness, whereas KTI did not reduce invasion of the Y529F cells
Khalil et al., J Biol Chem 2005
(MAP Kinase Signaling System) :
Proliferation of pulmonary interstitial fibroblasts is mediated by
transforming growth factor-beta1 induced release of extracellular fibroblast growth factor-2 and phosphorylation of p38
MAPK and JNK
Itagaki et al., Gut 2005
:
Oestradiol inhibited ROS generation and antioxidant enzyme loss via the suppression of NADH/NADPH oxidase activity, and attenuated hydrogen peroxide induced
transforming growth factor-beta1 ( TGF-beta1 ) expression, HSC proliferation and transformation, and the
activation of
mitogen activated protein kinase ( MAPK ) pathways and transcription factors
McGillicuddy et al., Vascul Pharmacol 2006
(Coronary Restenosis...) :
Fluvastatin abolished
TGF-beta1 induced phosphorylation of p38
MAPK and TGF-beta1 induced TSP-1 expression
Pelaia et al., J Cell Physiol 2007
(MAP Kinase Signaling System) :
Within such a context, the aim of our study was to investigate, in primary cultures of normal and fibrotic human lung fibroblasts ( HLFs ), the
effects of
TGF-beta1 on
mitogen activated protein kinase ( MAPK ) phosphorylation, cell proliferation, and production of interleukins 6 (IL-6) and 11 ( IL-11 ), in the presence or absence of a pretreatment with budesonide ( BUD ) ...
TGF-beta1 ( 10 ng/ml ) significantly
stimulated MAPK phosphorylation ( P < 0.01 ), and also enhanced cell proliferation as well as the secretion of both IL-6 and IL-11, which reached the highest increases at the 72nd h of cell exposure to this growth factor
Ferrari et al., Proc Natl Acad Sci U S A 2006
:
Inhibition of VEGF signaling through VEGF receptor 2 ( flk-1 ) abrogates
TGF-beta1 induced apoptosis and p38 (
MAPK ) activation ... Inhibition of p38 ( MAPK ) blocks TGF-beta1 induced apoptosis, showing that VEGF/flk-1 mediated activation of p38 (
MAPK ) is
required for
TGF-beta1 induction of apoptosis
Gui et al., Dig Dis Sci 2007
:
Furthermore, emodin markedly inhibited
TGFbeta1 induced p42/p44
mitogen activated protein kinase phosphorylation but did not alter PMA induction
Kim et al., American journal of physiology. Renal physiology 2007
:
TGF-beta activated kinase 1 and TAK1 binding protein 1 cooperate to mediate
TGF-beta1 induced MKK3-p38
MAPK activation and stimulation of type I collagen ... Transient overexpression of TAK1 with TAB1
enhanced the activation of MKK3 and p38
MAPK with or without TGF-beta(1) stimulation, whereas a dominant negative mutant of TAK1 ( TAK1DN ) suppressed
TGF-beta(1) induced activation of MKK3 and p38 MAPK
Luo et al., Zhonghua Yi Xue Za Zhi 2006
:
The present study was designed to evaluate the
role of
MAPK/ERK1/2 phosphorylation in mediating the synthesis of
TGF-beta1 in renal tubular epithelial cells that was activated by aldosterone
Huang et al., Kidney Int 2007
:
Renin stimulated
TGF-beta1 expression is
regulated by a
mitogen activated protein kinase in mesangial cells
Vásquez et al., J Cell Physiol 2007
:
TGF-beta1 and high D-glucose
increased p42/44(mapk) and Smad2 phosphorylation, an effect blocked by PD-98059 ( MEK1/2 inhibitor )
Hu et al., Am J Physiol Heart Circ Physiol 2007
(Anoxia...) :
TGF-beta(1) overexpression also
blocked H-R mediated p38 and p44/42
MAPK activation
Wang et al., Biochem Biophys Res Commun 2008
:
Meanwhile,
TGF-beta1 stimulated the phosphorylation of Akt and
extracellular signal regulated kinase 1/2 ( ERK1/2 )
Cailotto et al., Arthritis Res Ther 2007
(Chondrocalcinosis...) :
Induction of Ank by
TGF-beta1 required activation of the extracellular signal regulated kinase ( ERK ) pathway but not of
p38-mitogen activated protein kinase or of protein kinase A
Akel et al., Platelets 2007
(Leukemia, Erythroblastic, Acute...) :
Stable over-expression of Smad7 in K562 cells ( K562/7 ) prevented
activation of Smad2/3 and
MAPK ( ERK1/2, p38 and JNK1/2 ) proteins by
activin-A/TGF-beta1 and subsequent induction of erythroid differentiation
Pechkovsky et al., J Biol Chem 2008
(MAP Kinase Signaling System) :
In addition, echistatin inhibited
TGFbeta1 induced p38
MAPK but not Smad3 activation ... Furthermore, inhibition of the Src family kinases, but not focal adhesion kinase, completely abrogated
TGFbeta1 induced expression of alphavbeta3 and p38
MAPK phosphorylation but not beta5 integrin expression and Smad3 activation
Miller et al., Mol Cell Biol 2008
(Disease Progression...) :
Sphingosine kinases and sphingosine-1-phosphate are critical for
transforming growth factor beta induced
extracellular signal regulated kinase 1 and 2 activation and promotion of migration and invasion of esophageal cancer cells
Ding et al., J Biol Chem 2008
(Disease Models, Animal...) :
FRNK overexpression blocks
TGF-beta1 induced ERK or p38
MAPK activation in the presence, and surprisingly, in the absence of FAK
Bhaskaran et al., Proteomics 2008
:
Systemic analysis of TGFbeta proteomics revealed involvement of Plag1/CNK1/RASSF1A/Src network in
TGFbeta1 dependent
activation of
Erk1/2 and cell proliferation ... Network analysis demonstrated importance of a Plag1/CNK1/RASSF1A/Src dependent prozone effect, as a systemic feature which is crucial for
TGFbeta1 dependent activation of
Erk1/2 and regulation of cell proliferation
Zimpelmann et al., American journal of physiology. Renal physiology 2009
(MAP Kinase Signaling System) :
Stimulation of p38
MAPK phosphorylation by Ang- ( 1-7 )
leads to release of arachidonic acid and production of
TGF-beta1 and extracellular matrix proteins
Han et al., J Korean Med Sci 2009
(MAP Kinase Signaling System) :
We examined the
role of
extracellular-signal regulated kinase 1 and 2 ( ERK1/2 ), c-Jun N-terminal kinase (JNK) and activator protein-1 (AP-1) in the aldosterone induced
TGF-beta(1) expression in rat mesangial cells
Krug et al., Hypertension 2010
:
MR blockade and extracellular signal regulated kinase 1/2
mitogen activated protein kinase inhibition
prevent age associated increases of
transforming growth factor-beta , intercellular adhesion molecule 1, and procollagen 1
Leenders et al., J Biol Chem 2010
(Hypertrophy, Left Ventricular) :
We show that
transforming growth factor-beta mediated
activation of p38
MAPK is necessary and sufficient to decrease KLF15 expression
Kwon et al., J Endod 2010
:
TGFbeta1 induced cell migration and
increased the phosphorylation of Hsp27 and p38
MAPK in MDPC-23 cells
Wei et al., Cell Biol Int 2013
:
Our present study is to explore the role of AEG-1 in
TGF-beta1 induced p38
MAPK activation and EMT process in human renal tubular epithelial ( HK-2 ) cells
Hartsough et al., J Biol Chem 1995
:
We report here that both
TGF-beta 1 and TGF-beta 2
resulted in a rapid activation of mitogen activated protein kinase ( MAPK )
p44mapk , occurring within 5-10 min of growth factor addition
Berrou et al., Biochem J 1996
:
Transforming growth factor beta 1 inhibits
mitogen activated protein kinase induced by basic fibroblast growth factor in smooth muscle cells
Reimann et al., FEBS Lett 1997
:
Transforming growth factor-beta1 induces activation of Ras, Raf-1, MEK and
MAPK in rat hepatic stellate cells
Axmann et al., Biochem Biophys Res Commun 1998
:
Inhibition of the binding of growth factors to their tyrosine kinase receptors did not affect
MAPK activation by
TGF-beta1 ... It is shown that calcium dependent isoforms of PKC are required for
MAPK activation by
TGF-beta1