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RAC1 — SRC
Pathways - manually collected, often from reviews:
-
BioCarta links between pyk2 and map kinases:
PYK2/SRC/P130cas/CRKL complex (PTK2B-SRC-BCAR1-CRKL)
→
RAC1
(modification, activates)
-
BioCarta angiotensin ii mediated activation of jnk pathway via pyk2 dependent signaling:
PYK2/SRC/P130cas/CRKL complex (PTK2B-SRC-BCAR1-CRKL)
→
RAC1
(modification, activates)
-
KEGG Adherens junction:
SRC
→
RAC1/RAC2/RAC3
(protein-protein, indirect effect)
-
NCI Pathway Database Signaling events mediated by focal adhesion kinase:
RAC1/GDP complex (RAC1)
→
FAK/Src-Yes-Fyn/p130 CAS/CRK/DOCK1/ELMO1 complex (PTK2-YES1_SRC_FYN-BCAR1-CRK-DOCK1-ELMO1)
(modification, collaborate)
Cho et al., J Cell Biol 2002, Hsia et al., J Cell Biol 2003, Sharma et al., BMC cell biology 2008, Kiyokawa et al., Genes Dev 1998, Dolfi et al., Proc Natl Acad Sci U S A 1998
Evidence: mutant phenotype, physical interaction
-
Reactome Reaction:
SRC
→
RAC1
(reaction)
Brugnera et al., Nat Cell Biol 2002, 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, Li et al., Nat Neurosci 2008, Briançon-Marjollet et al., Mol Cell Biol 2008, Yoo et al., Mol Cells 2010
-
Reactome Reaction:
SRC
→
RAC1
(indirect_complex)
Zhang et al., J Cell Biol 2003, Marston et al., Nat Cell Biol 2003, Li et al., Nat Neurosci 2008, Briançon-Marjollet et al., Mol Cell Biol 2008
-
WikiPathways Robo4 and VEGF Signaling Pathways Crosstalk:
SRC
→
RAC1
(activation)
Text-mined interactions from Literome
Marignani et al., J Cell Biol 2001
:
Vav2 nucleotide exchange is Src dependent in vivo, since the coexpression of Vav2 and dominant negative
Src , or treatment with the Src inhibitor PP2,
blocks both Vav2 dependent
Rac activation and lamellipodia formation
Hsia et al., J Cell Biol 2003
(Neoplasm Invasiveness...) :
Cell invasion was linked to transient FAK accumulation at lamellipodia, formation of a
FAK-Src-p130Cas-Dock180 signaling complex, elevated
Rac and c-Jun NH2-terminal kinase
activation , and increased matrix metalloproteinase expression and activity
Servitja et al., J Biol Chem 2003
(Cell Transformation, Neoplastic) :
Evidence of a role for Tiam1 and Vav2 in
Rac activation by
Src
Shimizu et al., J Biochem 2003
:
Nectin furthermore
induces activation of Cdc42 and
Rac small G proteins through
c-Src , which eventually regulates formation of the cadherin based adherens junctions through reorganization of the actin cytoskeleton, gene expression through activation of a mitogen activated protein kinase cascade, and cell polarization through cell polarity proteins
Sato et al., Cancer Sci 2005
:
The activation of Cdc42 and
Rac by the trans-interaction of nectin and nectin is
mediated by
c-Src , another small G protein, Rap1, a Cdc42-GEF, FRG, and a Rac-GEF, Vav2
Oh et al., Oncogene 2006
:
Therefore, TIMP-2 mediated inhibition of
Src kinase activity
leads to the signaling switch from
Rac1 to Rap1, thereby leading to enhanced RECK expression
Chaturvedi et al., J Biol Chem 2007
:
Src inhibition
blocked strain induced
Rac1 phosphorylation, but Rac inhibition did not alter Src phosphorylation
Murata et al., J Neurosci 2006
:
CD47 promotes neuronal development through
Src- and FRG/Vav2 mediated
activation of
Rac and Cdc42 ... These results indicate that CD47 promotes development of dendrites and axons in hippocampal neurons in a manner dependent, at least in part, on activation of Cdc42 and
Rac mediated by
Src as well as by FRG and Vav2
Nomura et al., Int J Mol Med 2007
(Glioblastoma) :
These results indicated that
Src might
regulate the subcellular localization of
Rac1 through phosphorylation of Crk
Dise et al., Am J Physiol Gastrointest Liver Physiol 2008
:
Epidermal growth factor stimulates
Rac activation through
Src and phosphatidylinositol 3-kinase to promote colonic epithelial cell migration
Chaudhry et al., Cell Host Microbe 2007
(HIV Infections) :
At the cell surface,
Src promotes
Rac activation via TIAM, a guanine nucleotide exchange factor for Rac
Zhao et al., J Lipid Res 2009
(Neovascularization, Pathologic...) :
15 ( S ) -HETE stimulated
Src in HRMVEC in a time dependent manner and blockade of its activation
inhibited 15 ( S ) -HETE induced
Rac1 stimulation in HRMVEC and the migration and tube formation of these cells as well as Matrigel plug angiogenesis
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
Binker et al., Biochem Biophys Res Commun 2009
(Neoplasm Invasiveness...) :
Our results also indicate that signaling events downstream of EGF receptor involved PI3K- and
Src dependent activation of
Rac1 , which mediated the NADPH generated reactive oxygen species responsible for MMP-2 secretion and activation
Putnam et al., Cell communication and signaling : CCS 2009
:
Src had no effect on
Rac activity
Guidetti et al., Journal of thrombosis and haemostasis : JTH 2009
:
Integrin alpha2beta1 recruitment triggered the
Src kinase independent
activation of the small GTPase
Rac1 , and activation of Rac1 was not required for PLCgamma2 phosphorylation
Nerlich et al., J Biol Chem 2009
(Streptococcal Infections) :
Invasion of endothelial cells by tissue-invasive M3 type group A streptococci requires
Src kinase and
activation of
Rac1 by a phosphatidylinositol 3-kinase independent mechanism
Zhang et al., Antioxid Redox Signal 2010
:
ROS generation,
Rac1 activation, and p67(phox) membrane translocation were also
prevented by
Src inhibition
Lee et al., Carcinogenesis 2011
(Anoxia) :
Using biochemical and genetic inhibition, we demonstrated that
Src requires reduced nicotinamide adenine dinucleotide phosphate ( NADPH )
oxidase/Rac complex for stabilization of HIF-1a
Neri et al., Blood 2011
(Multiple Myeloma...) :
In addition, ITGB7 silencing abrogated MM-cell transwell migration in response to SDF1a gradients, reduced vessel density in xenografted tumors, and altered MM cells in vivo homing into the BM. Mechanistically, ITGB7 knockdown inhibited focal adhesion kinase ( FAK ) and
Src phosphorylation,
Rac1 activation , and SUMOylation, reduced VEGF production in MM-BM stem cell cocultures and attenuated p65-NF-?B activity
Huang et al., J Biol Chem 2011
:
Here, we show that ARV induced phosphorylation of caveolin-1 ( Tyr ( 14 ) ), dynamin-2 expression, and
Rac1 activation through activation of p38 MAPK and
Src in the early stage of the virus life cycle is beneficial for virus entry and productive infection
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 ... 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
Singh et al., Blood 2011
(Ischemia) :
15 ( S ) -HETE by inducing HMG-CoA reductase expression caused increased farnesylation and membrane translocation of
Rac1 where it became activated by
Src dependent aPix stimulation
Kant et al., Genes Dev 2011
(Inflammation) :
This signaling pathway requires
Src dependent
activation of the guanosine nucleotide exchange factor Vav, activation of
Rac/Cdc42 , and the engagement of the Rac/Cdc42 interaction site ( CRIB motif ) on mixed-lineage protein kinases ( MLKs )
Ren et al., Cell Physiol Biochem 2012
:
Periodic mechanical stress activates integrinß1 dependent
Src dependent PLC?1 independent
Rac1 mitogenic signal in rat chondrocytes through ERK1/2 ... In addition, inhibition of
Src with its selective inhibitor PP2 and shRNA targeted to Src
blocked Rac1 signal activation ( p < 0.05 for each ), but inhibition of the activity of PLC?1 did not affect the phosphorylation and activation levels of Rac1 under conditions of periodic mechanical stress
Song et al., Journal of neuroinflammation 2012
(Neuroblastoma) :
In addition, we found that
Src activation could
enhance Rac1 activity and F-actin accumulation that typify microglial phagocytic activity ... We also found that
Src/PI3K/Akt inhibitors prevented LLLT stimulated Akt ( Ser473 and Thr308 ) phosphorylation and
blocked Rac1 activity and actin based microglial phagocytosis, indicating the activation of Src/PI3K/Akt/Rac1 signaling pathway
Koch et al., Neurobiol Dis 2013
:
This correlates with the reggie-1 dependent
activation of
Src and PI3 kinase (PI3K), of the Rho family GTPase
Rac1 and downstream effectors such as cofilin
Gomes et al., PloS one 2013
:
The characterization of downstream molecular targets of c-Met activation, involved in the invasive phenotype, revealed increased phosphorylation of FAK and
Src proteins and
activation of Cdc42,
Rac1 and RhoA GTPases