◀ Back to MAPK1
MAPK1 — SRC
Pathways - manually collected, often from reviews:
-
OpenBEL Selventa BEL large corpus:
MAPK1
→
SRC
(increases)
Chaturvedi et al., J Biol Chem 2007*
Evidence: Src or Rac1 inhibition also prevented strain-induced FAK phosphorylation at Tyr(576) and ERK phosphorylation but not FAK phosphorylation at Tyr(397).
-
NCI Pathway Database Signaling events mediated by focal adhesion kinase:
FAK/Src-Yes-Fyn/ERK2/m-calpain complex (PTK2-YES1_SRC_FYN-MAPK1-CAPN2)
→
ERK2 (MAPK1)
(modification, collaborate)
Cuevas et al., EMBO J 2003, Carragher et al., Curr Biol 2003, Westhoff et al., Mol Cell Biol 2004, Sawhney et al., J Biol Chem 2006
Evidence: assay, physical interaction, other species
-
NCI Pathway Database Signaling events mediated by focal adhesion kinase:
FAK/Src-Yes-Fyn/ERK2/m-calpain complex (PTK2-YES1_SRC_FYN-MAPK1-CAPN2)
→
FAK/Src-Yes-Fyn complex (PTK2-YES1_SRC_FYN)
(modification, collaborate)
Cuevas et al., EMBO J 2003, Carragher et al., Curr Biol 2003, Westhoff et al., Mol Cell Biol 2004, Sawhney et al., J Biol Chem 2006
Evidence: assay, physical interaction, other species
-
NCI Pathway Database Signaling events mediated by focal adhesion kinase:
FAK/Src-Yes-Fyn/ERK2/m-calpain complex (PTK2-YES1_SRC_FYN-MAPK1-CAPN2)
→
m-calpain (CAPN2)
(modification, collaborate)
Cuevas et al., EMBO J 2003, Carragher et al., Curr Biol 2003, Westhoff et al., Mol Cell Biol 2004, Sawhney et al., J Biol Chem 2006
Evidence: assay, physical interaction, other species
-
NCI Pathway Database Signaling events mediated by focal adhesion kinase:
ERK2 (MAPK1)
→
FAK/Src-Yes-Fyn complex (PTK2-YES1_SRC_FYN)
(modification, collaborate)
Cuevas et al., EMBO J 2003, Carragher et al., Curr Biol 2003, Westhoff et al., Mol Cell Biol 2004, Sawhney et al., J Biol Chem 2006
Evidence: assay, physical interaction, other species
-
Reactome Reaction:
MAPK1
→
SRC
(direct_complex)
Kuo et al., Cell Signal 2006, Luttrell et al., Science 1999*
-
Reactome Reaction:
MAPK1
→
SRC
(reaction)
Kuo et al., Cell Signal 2006, Luttrell et al., Science 1999*
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
Text-mined interactions from Literome
Della Rocca et al., J Biol Chem 1999
:
In all three cell types, GPCR stimulated
Erk 1/2 activation is significantly
inhibited by the
Src kinase inhibitors, herbimycin A and 4-amino-5- ( 4-methylphenyl ) -7- ( t-butyl ) pyrazolo-D-3,4-pyrimidine ( PP1 ), suggesting that Src family nonreceptor tyrosine kinases represent a point of convergence for signals originating from either scaffold
Daly et al., Oncogene 1999
:
All three ligands induced short-term activation of p38
MAPK in a
c-Src dependent manner
Munshi et al., J Immunol 2000
(MAP Kinase Signaling System...) :
Further studies using mutants of c-Src kinase revealed that
Src mediates
mitogen activated protein kinase activation induced by VEGF
Nebigil et al., Proc Natl Acad Sci U S A 2000
(MAP Kinase Signaling System) :
Inhibition of
c-Src activity by 4-amino-5- ( 4-methylphenyl ) -7- ( t-butyl ) pyrazolo [ 3,4-d ] pyrimidine ( PP1 ) or depletion of c-Src is
sufficient to abolish the 5-HT induced ( i ) PDGFR tyrosine kinase phosphorylation and
MAPK activation, ( ii ) cyclin D1 and cyclin E expression levels, and ( iii ) thymidine incorporation
Graness et al., Biochem J 2000
:
Although Src does not participate in bradykinin induced stimulation of PTP activity, inhibition of
Src by 4-amino-5- ( 4-methylphenyl ) -7- ( t-butyl ) pyrazolo ( 3,4-d ) pyrimidine
leads to an increase in
MAPK activation by bradykinin
Schmid et al., J Neurosci 2000
(MAP Kinase Signaling System...) :
The nonreceptor tyrosine kinase
pp60(c-src) was
required for L1-triggered
MAPK phosphorylation, as shown in src-minus cerebellar neurons and by expression of the kinase-inactive mutant Src ( K295M ) in B35 neuroblastoma cells
Bondzi et al., Cell Growth Differ 2000
(Carcinoma, Small Cell...) :
Src family kinase activity is
required for Kit mediated
mitogen activated protein ( MAP ) kinase activation, however loss of functional retinoblastoma protein makes MAP kinase activation unnecessary for growth of small cell lung cancer cells
Robinson et al., Eur J Pharmacol 2001
:
The
Src tyrosine kinase inhibitor PP2 ( 4-amino-5- ( 4-chlorophenyl ) -7- ( t-butyl ) pyrazolo [ 3,4-d ] pyrimidine ) and the epidermal growth factor receptor tyrosine kinase inhibitor AG1478 ( 4- ( 3-chloroanilino ) -6,7-dimethoxyquinazoline ) also
had no effect on adenosine A(1) receptor stimulation of p42/p44
MAPK
Cammarota et al., J Neurochem 2001
(MAP Kinase Signaling System) :
Our data support the hypothesis that in BACC, AII upregulates CREB functionality through a mechanism that requires
Src mediated
activation of
ERK 1/2 and ( p90 ) RSK
Simeonova et al., Mol Cell Biochem 2002
:
One of this pathways might include
c-Src dependent EGFR and
MAPK activation
Xu et al., Am J Pathol 2002
:
Both a protein kinase C inhibitor, GF109203X, and a
Src inhibitor, PP1,
attenuated 5-HT stimulated
Erk 1/2 activation
Xiang et al., Zhejiang Da Xue Xue Bao Yi Xue Ban 2003
:
To further clarify the mechanism of Ang II-induced intracellular signal transduction in vascular smooth muscle cells ( VSMCs ) proliferation by observing the
effect of
c-Src on Ang II-mediated
MAPK activation and c-fos protein expressions in rat VSMCs
Acosta et al., Mol Endocrinol 2003
:
We initially observed that PRL dependent activation of focal adhesion kinase ( Fak ),
Erk1/2 , and cell proliferation was
mediated by
c-Src in T47D cells, because expression of a dominant negative form of c-Src ( SrcDM, K295A/Y527F ) blocked the PRL dependent effects
Khadaroo et al., Surgery 2003
:
Oxidant stress generated during global ischemia/reperfusion activates p38
MAPK in an
Src dependent manner
Recchia et al., Bone 2004
(Adenocarcinoma, Clear Cell...) :
c-Src inhibition
stabilized p38
mitogen activated protein kinase ( MAPK ), whereas the c-Jun N-terminal kinase (JNK) pathway did not appear to be modulated by our compounds
Tejedo et al., Endocrinology 2004
:
In addition, we found that NO produces
c-Src/PI3K- and PKG dependent
activation of
ERK 1/2
Tsuruda et al., FEBS Lett 2004
(MAP Kinase Signaling System...) :
Constitutively active
Src facilitates NGF induced phosphorylation of TrkA and
causes enhancement of the
MAPK signaling in SK-N-MC cells
Salinthone et al., Am J Physiol Gastrointest Liver Physiol 2004
(Inflammation) :
Expression of IL-1beta, IL-6, IL-8, and COX-2 mRNA was reduced by 30 microM PP1, an
Src family tyrosine kinase inhibitor, and by 25 microM SB-203580, a p38
MAPK inhibitor
Waters et al., Cell Signal 2005
:
Indeed, the PDGF dependent activation of p42/p44
MAPK was
reduced by over-expression of the C-terminal domain of GRK2 ( sequesters Gbetagamma subunits ), the clathrin binding domain of beta-arrestin and by inhibitors of
c-Src and clathrin mediated endocytosis
Amos et al., J Biol Chem 2005
(Glioblastoma) :
The effects of PMA on
MAPK phosphorylation and glioblastoma cell proliferation were
reduced by BIM, rottlerin, the MEK inhibitor U0126, and PKCdelta and
c-Src siRNAs
Callera et al., Hypertension 2005
:
We tested the hypothesis that aldosterone induces activation of vascular
mitogen activated protein ( MAP ) kinases and NADPH oxidase via
c-Src dependent mechanisms in vascular smooth muscle cells ( VSMCs )
Zhou et al., Toxicological sciences : an official journal of the Society of Toxicology 2005
:
MAPK phosphorylation by two other translational inhibitors, anisomycin and emetine, were similarly
Src dependent
Zubkov et al., J Cardiovasc Pharmacol 2004
:
The following results were observed : ( 1 ) endothelin-1 produced phosphorylation of MAPK and RhoA and contraction by activation of endothelin-A but not endothelin-B receptors ; ( 2 )
MAPK inhibitors, PD 98059 and U0126, PTK inhibitor, genistein,
Src kinase
inhibitor , damnacanthal, and Janus tyrosine kinase ( JAK2 ) inhibitor, AG-490, abolished endothelin-1 induced contraction and MAPK immunoreactivity ; ( 3 ) PTK inhibitor, staurosporine, and phosphatidylinositol 3-kinase (PI- 3K) inhibitor wortmannin abolished endothelin-1 induced contraction but not MAPK immunoreactivity ; ( 4 ) Rho-kinase inhibitor, Y-27632, reduced endothelin-1 induced contraction ; ( 5 ) PI-3K inhibitor, wortmannin, but not PKC and PTK inhibitors, reduced endothelin-1 induced RhoA activation ; ( 6 ) endothelin-1 increased the level of myosin light chain ( MLC ) phosphorylation, and Rho-kinase inhibitor, Y-27632, reduced the effect of endothelin- 1 on MLC phosphorylation
Wei et al., J Biol Chem 2005
(MAP Kinase Signaling System) :
However, deletion of this region in the context of human RON enhanced receptor phosphorylation,
activation of
mitogen activated protein kinase , and association of
c-Src at levels comparable with those observed with mouse RON
Gelain et al., Cell Signal 2006
:
In this work, we report that, in Sertoli cells, retinol ( 7 microM ) induces the
Src dependent
activation of ERK1/2
MAPK and the ERK1/2 mediated phosphorylation of the transcription factor CREB
Simó et al., Cereb Cortex 2007
(MAP Kinase Signaling System) :
The inhibition of
Src family kinases (SFK) blocked Reelin dependent
Erk1/2 activation
Carini et al., J Hepatol 2006
(Anoxia...) :
ATPgammaS activated Src and promoted a
Src dependent stimulation of both ERK1/2 and
p38MAPK
Pardo et al., Biogerontology 2007
:
Extracellular and intracellular Ca ( 2+ ) chelation or
c-Src pharmacological inhibition
suppressed hormone activation of p38
MAPK in both, young and aged rats, demonstrating that Ca ( 2+ ) and the non-receptor tyrosine kinase c-Src are required for full activation of p38 MAPK in cells stimulated with 1alpha,25 ( OH ) ( 2 ) D ( 3 )
Galliher et al., Breast Cancer Res 2006
(Breast Neoplasms...) :
Inhibiting
Src activity in MECs
prevented the ability of beta3 integrin to induce TbetaR-II tyrosine phosphorylation,
MAPK activation, and EMT stimulated by TGF-beta
Hodges et al., Invest Ophthalmol Vis Sci 2006
:
Roles of protein kinase C, Ca2+, Pyk2, and
c-Src in agonist activation of rat lacrimal gland p42/p44
MAPK
Fleming et al., Endocrinology 2006
:
Unexpectedly, inhibition of
Src increased basal
MAPK activation
Faivre et al., Mol Cell Biol 2007
(Breast Neoplasms) :
Progesterone receptors upregulate Wnt-1 to induce epidermal growth factor receptor transactivation and
c-Src dependent sustained activation of
Erk1/2 mitogen activated protein kinase in breast cancer cells
Cheng et al., Endocrinology 2007
:
In addition, we demonstrate that Src kinase is activated by T and that
Src kinase activity is
required for stimulation of the ERK
MAPK and CREB
Jin et al., Cancer Res 2007
(Cell Transformation, Neoplastic) :
Suppression of
c-Src by RNA interference in NIH3T3-ETV6-NTRK3 cells
resulted in markedly decreased expression of cyclin D1 and suppression of activation of
Ras-Erk1/2 and PI3K-Akt
Galliher et al., Cancer Res 2007
(MAP Kinase Signaling System...) :
Src phosphorylates Tyr284 in TGF-beta type II receptor and
regulates TGF-beta stimulation of p38
MAPK during breast cancer cell proliferation and invasion
Yaghini et al., J Biol Chem 2007
:
These data suggest that Syk expressed in VSMC is activated by Ang II through p38
MAPK activated
c-Src subsequent to cytosolic phospholipase A ( 2 ) and generation of AA metabolites via LO, and it mediates Ang II-induced protein synthesis independent of epidermal growth factor receptor transactivation ( Ang II -- > cPLA(2) -- > AA metabolites of LO -- > p38 MAPK -- > c-Src -- > Syk -- > protein synthesis )
Lim et al., Arch Biochem Biophys 2007
(MAP Kinase Signaling System) :
Inhibition of
c-Src suppressed Raf/MEK/ERK pathway but
activated p38
MAPK ... Inhibition of p38
MAPK did not
affect c-Src activity in PM
Jin et al., J Biol Chem 2008
(Cell Transformation, Neoplastic) :
Suppression of
c-Src by RNA interference in highly metastatic 4T1 mammary cancer cells, which express endogenous TrkC,
resulted in markedly decreased expression of cyclin D1 and suppression of activation of
Ras-Erk1/2 and PI3K-Akt
Slomiany et al., Inflammopharmacology 2008
:
Our findings demonstrate that leptin protection of salivary gland acinar cells against ethanol cytotoxicity involves
Src kinase
mediated parallel activation of
MAPK/ERK and Akt that result in up-regulation of the respective prostaglandin and nitric oxide synthase pathways
Eblin et al., Toxicology 2008
:
To determine importance of ROS in the
MAPK cascade and its downstream
induction of
p-Src and COX-2, specific ROS antioxidants ( both enzymatic and non-enzymatic ) were used concomitantly with arsenicals
Chaturvedi et al., Mol Cell Biochem 2008
:
Src inhibition
increased mitogen activated protein kinase phosphatase-1 protein and decreased phosphorylation of SF-1, which correlated with increased CYP17 promoter activity and mRNA levels
Holmström et al., Exp Cell Res 2008
(MAP Kinase Signaling System) :
EGF stimulated Erk1/2 activation involved Src tyrosine kinases, but not PKC or PI3K, whereas in PDGF induced
Erk1/2 activation, PI3K, PKC ( probably the atypical zeta isoform ) and
Src were
involved sequentially
Kim et al., Mol Cancer Res 2008
(MAP Kinase Signaling System...) :
Inhibition of
c-Src by pretreatment with Src family kinase inhibitor PP2 or small interfering RNA targeting of c-Src
attenuated radiation induced p38
MAPK and Rac1 activation and enhanced Bax and Bak activation and cell death
Kim et al., Mol Cancer Res 2008
(MAP Kinase Signaling System...) :
Inhibition of
c-Src attenuated Rac1 and p38
MAPK activations and Ser ( 473 ) phosphorylation of Akt
Schweppe et al., J Clin Endocrinol Metab 2009
(Carcinoma...) :
Phospho-ERK1/2 was not affected by AZD0530, indicating that
Src signaling does not
require MAPK
Chai et al., IUBMB Life 2009
:
The current study investigated a possible
role for p38
MAPK in the regulation of (
SRC ) -3 phosphorylation/degradation and in retinoic acid receptor (RAR)alpha signaling in mouse fetal cortical neurons treated with all-trans retinoic acid ( ATRA )
Feng et al., Oncogene 2009
(Carcinoma, Renal Cell...) :
Strikingly, silencing of Cbp negatively affected the sustaining of
Erk1/2 activation but not
c-Src activation induced by serum
Watanabe et al., Mol Cancer Res 2009
(Sarcoma, Synovial) :
Adaptor protein Crk induces
Src dependent activation of p38
MAPK in regulation of synovial sarcoma cell proliferation
Hsieh et al., Neurotox Res 2010
:
Taken together, these results suggested that in RBA-1 cells, activation of NF-kappaB by a
c-Src dependent PI3K/Akt-p42/p44
MAPK activation mediated through transactivation of PDGFR is essential for MMP-9 gene upregulation induced by LTA
Zhang et al., Biochem Pharmacol 2010
(Breast Neoplasms...) :
By contrast, S3I-201.1066 has no effect on
Src activation or the EGFR mediated
activation of the Erk1/2 (
MAPK ) pathway
Ronda et al., J Steroid Biochem Mol Biol 2010
:
Role of estrogen receptors, PKC and
Src in ERK2 and p38
MAPK signaling triggered by 17ß-estradiol in skeletal muscle cells
Vallabhaneni et al., Breast Cancer Res Treat 2011
(Breast Neoplasms) :
Depletion of
Src using shRNA substantially
reduced E2 mediated activation of Src and
MAPK activation in resistant model cells
Arpaia et al., Oncogene 2012
(Neoplasm Metastasis...) :
Our data indicate that interaction between Cav1 and Rho-GTPases ( most likely RhoC but not RhoA ) promotes metastasis by stimulating a5-integrin expression and regulating the
Src dependent activation of p130 ( Cas ) /Rac1, FAK/Pyk2 and
Ras/Erk1/2 signaling cascades
Lei et al., Am J Physiol Lung Cell Mol Physiol 2011
:
In summary, in adult rat AECs T3-stimulated
Src kinase activity can
activate both PI3K/Akt and
MAPK/ERK1/2 , and activation of Akt is necessary for T3-induced Na-K-ATPase activity
Bhattacharjee et al., J Biol Chem 2011
(MAP Kinase Signaling System) :
Our data show that
Src kinase activity
regulates IL-13 induced p38
MAPK tyrosine phosphorylation via the upstream kinases MKK3 or MKK6
Duru et al., J Surg Res 2012
:
Src inhibition with PP2
reduced p38 (
MAPK ) and JNK activation but did not alter ERK1/2 activation
Lopez et al., Cell Death Differ 2012
(MAP Kinase Signaling System...) :
Importantly, in a set of human cancer cells with
Src- , Kras- or BRAF dependent
activation of
Erk1/2 , resistances to staurosporine or thapsigargin were also shown to depend on Bik degradation rate via a similar mechanism
Castillo-Sanchez et al., Cell Biol Toxicol 2013
(Breast Neoplasms...) :
Here, we demonstrate that B [ a ] P induces cell migration through a lipoxygenase- and
Src dependent pathway, as well as the activation of focal adhesion kinase, Src, and the
extracellular signal regulated kinase 2 in MDA-MB-231 breast cancer cells
Abe et al., J Biol Chem 1997
:
c-Src is
required for oxidative stress mediated activation of big
mitogen activated protein kinase 1
Liu et al., Mol Cell Biol 1998
(Cell Transformation, Neoplastic) :
Expression of WT-PTP1B reduces formation of p130Cas-Crk complexes and inhibits
mitogen activated protein kinase activation by
Src and Crk