◀ Back to PIK3R1
PIK3R1 — RAC1
Pathways - manually collected, often from reviews:
-
KEGG VEGF signaling pathway:
PIK3CA/PIK3CB/PIK3CD/PIK3CG/PIK3R1/PIK3R2/PIK3R3/PIK3R5
→
RAC1/RAC2/RAC3
(protein-protein, compound)
-
KEGG Toll-like receptor signaling pathway:
RAC1
→
PIK3CA/PIK3CB/PIK3CD/PIK3CG/PIK3R1/PIK3R2/PIK3R3/PIK3R5
(protein-protein, activation)
-
KEGG Natural killer cell mediated cytotoxicity:
PIK3CA/PIK3CB/PIK3CD/PIK3CG/PIK3R1/PIK3R2/PIK3R3/PIK3R5
→
RAC1/RAC2/RAC3
(protein-protein, activation)
-
KEGG Fc epsilon RI signaling pathway:
PIK3CA/PIK3CB/PIK3CD/PIK3CG/PIK3R1/PIK3R2/PIK3R3/PIK3R5
→
RAC1/RAC2/RAC3
(protein-protein, activation)
-
KEGG Leukocyte transendothelial migration:
PIK3CA/PIK3CB/PIK3CD/PIK3CG/PIK3R1/PIK3R2/PIK3R3/PIK3R5
→
RAC1
(protein-protein, indirect effect)
-
NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met):
RAC1/GTP complex (RAC1)
→
PI3K complex (PIK3CA-PIK3R1)
(modification, inhibits)
Cozzolino et al., Mol Biol Cell 2003
Evidence: mutant phenotype
-
NCI Pathway Database Nongenotropic Androgen signaling:
RAC1-CDC42/GDP complex (RAC1_CDC42)
→
PI3K complex (PIK3CA-PIK3R1)
(modification, collaborate)
Papakonstanti et al., Mol Endocrinol 2003*
Evidence: assay
-
NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met):
RAC1/GDP complex (RAC1)
→
PI3K complex (PIK3CA-PIK3R1)
(modification, collaborate)
Royal et al., Mol Biol Cell 2000*, Ishibe et al., Mol Cell 2004*, Bosse et al., Mol Cell Biol 2007
Evidence: mutant phenotype
-
NCI Pathway Database Class I PI3K signaling events:
RAC1/GDP complex (RAC1)
→
PI3K Class IA family (PIK3CA/PIK3R1/PIK3CB/PIK3R1)
(modification, collaborate)
Hawkins et al., Curr Biol 1995*
Evidence: mutant phenotype
-
NCI Pathway Database a6b1 and a6b4 Integrin signaling:
Rac1b/GDP complex (RAC1)
→
PI3K complex (PIK3CA-PIK3R1)
(modification, collaborate)
Chartier et al., J Cell Sci 2006
Evidence: mutant phenotype, assay
-
NCI Pathway Database S1P2 pathway:
RAC1/GDP complex (RAC1)
→
PI3K complex (PIK3CA-PIK3R1)
(modification, collaborate)
Sugimoto et al., Mol Cell Biol 2003, Arikawa et al., J Biol Chem 2003, Gonda et al., Biochem J 1999
-
NCI Pathway Database Signaling events regulated by Ret tyrosine kinase:
RAC1/GDP complex (RAC1)
→
PI3K complex (PIK3CA-PIK3R1)
(modification, collaborate)
Maeda et al., Biochem Biophys Res Commun 2004, Asai et al., Development 2006*
Evidence: assay, other species
-
NCI Pathway Database Angiopoietin receptor Tie2-mediated signaling:
RAC1/GDP complex (RAC1)
→
PI3K complex (PIK3CA-PIK3R1)
(modification, collaborate)
Cascone et al., Blood 2003*
Evidence: mutant phenotype, assay
-
NCI Pathway Database Nephrin/Neph1 signaling in the kidney podocyte:
RAC1/GDP complex (RAC1)
→
PI3K Class IA family (PIK3CA/PIK3R1/PIK3CB/PIK3R1)
(modification, collaborate)
Zhu et al., Kidney Int 2008
Evidence: assay
-
NCI Pathway Database IL2 signaling events mediated by PI3K:
RAC1/GDP complex (RAC1)
→
PI3K complex (PIK3CA-PIK3R1)
(modification, collaborate)
Jiang et al., Blood 2003
Evidence: mutant phenotype
-
NCI Pathway Database Osteopontin-mediated events:
Rho Family GTPase-active (RHOA/CDC42/RAC1)
→
PI3K complex (PIK3CA-PIK3R1)
(modification, activates)
Biswas et al., BMC cell biology 2004*, Chellaiah et al., Mol Biol Cell 1996
Evidence: mutant phenotype, assay
-
NCI Pathway Database N-cadherin signaling events:
RAC1/GDP complex (RAC1)
→
PI3K complex (PIK3CA-PIK3R1)
(modification, collaborate)
Gavard et al., J Cell Sci 2004
Evidence: mutant phenotype, assay
-
Reactome Reaction:
PIK3R1
→
RAC1
(reaction)
Murga et al., Oncogene 2002*, Kovacsovics et al., J Biol Chem 1995*, Bokoch et al., Biochem J 1996*
-
Reactome Reaction:
PIK3R1
→
RAC1
(indirect_complex)
Murga et al., Oncogene 2002*, Kovacsovics et al., J Biol Chem 1995*, Bokoch et al., Biochem J 1996*
-
WikiPathways Rac1/Pak1/p38/MMP-2 pathway:
RAC1
→
PIK3R1
(activation)
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
Text-mined interactions from Literome
Nosaka et al., Biochem Biophys Res Commun 2001
(Fibrosarcoma) :
The
PI3K inhibitor LY294002 significantly
inhibited TNFalpha activation of
Rac as well as Erk and abolished that of the PI3K target Akt, without showing any inhibitory effects on JNK and p38 activation
Zeng et al., J Biol Chem 2002
:
As expected, CDC42 and
Rac1 activation mediated by EGLT can be completely
inhibited by
PI3K inhibitors, wortmannin and LY294002, and the p85 dominant negative mutant but not by either the phospholipase C inhibitor, or an intracellular Ca ( 2+ ) chilator BAPTA/AM
Inabe et al., J Exp Med 2002
:
The functional interaction between PI3K and Rac1 was also demonstrated by increased
PI3K activity in the
presence of GTP bound
Rac1
Nusser et al., J Biol Chem 2002
:
Furthermore, inhibition of
PI3K significantly
reduced NGF- mediated
Rac1 activation, whereas dominant negative Rac1 abolished the inhibitory signaling to RhoA
Kanda et al., Biochem Biophys Res Commun 2003
:
These results implicate CrkL in
PI3K dependent activation of
Rac by outside-in signaling from alpha4beta1 and suggest that adhesion through alpha4beta1 further activates cytokine receptor associated Jak2 to induce phosphorylation of these receptors
Welch et al., FEBS Lett 2003
(Second Messenger Systems) :
Vice versa,
Rac can also
stimulate the activation of
PI3K , although the mechanism for this is unclear
Alahari et al., Exp Cell Res 2003
:
Furthermore, Nischarin does not affect
Rac mediated JNK and
PI3K activities
Sánchez-Martín et al., J Biol Chem 2004
:
We have identified Vav, a guanine nucleotide exchange factor for Rac-1, and PI3K/Akt, as regulators of the activation and inactivation phases of the activity of Rac-1, respectively, in the context of LFA-1 signaling based on the following experimental evidence : ( i ) LFA-1 induced activation of Vav and
PI3K/Akt with kinetics consistent with a regulatory role for these molecules on Rac-1, ( ii ) overexpression of a constitutively active Vav mutant induces activation of Rac independently of LFA-1 stimulation whereas overexpression of a dominant negative Vav mutant
blocks LFA-1 mediated
Rac activation, ( iii ) pharmacological inhibition of PI3K/Akt prevented the fall in the activity of Rac-1 after its initial activation but had no effect on Vav activity, and ( iv ) overexpression of a dominant negative or a constitutively active Akt-1 induced or inhibited, respectively, Rac-1 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
Felekkis et al., Mol Cancer Res 2005
(Breast Neoplasms) :
Inhibition of
PI3K with LY294002 or a dominant negative p85 construct
blocked AND-34 mediated
Rac and Akt activation ... Our studies suggest that AND-34 mediated
PI3K activation
induces Rac activation and anti-estrogen resistance in human breast cancer cell lines
Krötz et al., J Am Coll Cardiol 2005
:
In HUVEC, SHP-1 counteracts basal and stimulated NAD ( P ) H-oxidase activity by negative regulation of
PI3K dependent
Rac1 activation ; SHP-1 thus seems to be an important part of endothelial antioxidative defense controlling the activity of the O2 ( *- ) -producing NAD ( P ) H-oxidase
Harokopakis et al., J Immunol 2006
:
A dominant negative mutant of
Rac1 also
inhibited the lipid kinase activity of
PI3K suggesting that Rac1 acts upstream of PI3K in this proadhesive pathway
Gouëffic et al., Cardiovasc Res 2006
:
Hyaluronan induces vascular smooth muscle cell migration through RHAMM mediated
PI3K dependent
Rac activation ... HA-induced migration depends exclusively on RHAMM mediated
PI3K dependent
Rac activation
Vanni et al., Cell cycle (Georgetown, Tex.) 2006
:
Inhibition of
PI3K induces
Rac activation and membrane ruffling in proto-Dbl expressing cells
Nielsen-Preiss et al., Endocrinology 2007
:
In addition,
PI3K inhibition in GnRH neuronal cells
diminished Gas6 induced
Rac activation
Nizhynska et al., Dev Neurobiol 2007
:
Moreover, agrin induced activation of
Rac and Cdc42 is
impaired in the presence of
PI3-K inhibitors
Babbin et al., J Immunol 2007
:
Taken together, theses results support a novel role for FPR stimulation in enhancing intestinal epithelial cell restitution through
PI3K dependent activation of
Rac1 and Cdc42
Muñoz-Alonso et al., J Pharmacol Exp Ther 2008
(Melanoma) :
Plitidepsin cytotoxicity diminishes by
Rac1 inhibition or by the blockage of JNK and p38 MAPK using 4- ( 4-fluorophenyl ) -2- ( 4-methylsulfinylphenyl ) -5- ( 4-pyridyl ) 1H-imidazole ( SB203580 ), but not by
PI3K inhibition using wortmannin or 2- ( 4-morpholinyl ) -8-phenyl-4H-1-benzopyran-4-one ( LY294002 )
Jiang et al., Hepatology 2008
:
We found that leptin induced the
PI3K dependent activation of
Rac1 , and that nicotinamide adenine dinucleotide phosphate, reduced form ( NADPH ) oxidase activation was also implicated in this process
Jeon et al., Pigment Cell Melanoma Res 2009
:
Our results demonstrated that SCF induced ERM proteins phosphorylation on threonine residue and
Rac1 activation in cultured normal human melanocytes through the activation of
PI3K
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
Binker et al., Biochem Biophys Res Commun 2009
(Pulmonary Disease, Chronic Obstructive) :
Our results also indicate that signaling events downstream of EGFR involved
PI3K dependent activation of
Rac1 , which mediated the NADPH generated reactive oxygen species responsible for MMP-9 secretion and activation
Samaga et al., PLoS Comput Biol 2009
(Liver Neoplasms) :
Our results strongly suggest that the
Rac/Cdc42 induced p38 and JNK cascades are
independent of
PI3K in both primary hepatocytes and HepG2
Hubchak et al., American journal of physiology. Renal physiology 2009
(Fibrosis) :
It also partially blocked active Rac1 stimulated collagen promoter activity, suggesting that
PI3K activity
contributes to both TGF-beta activation of
Rac1 and signal propagation downstream of Rac1
Xia et al., Journal of thrombosis and haemostasis : JTH 2010
:
Subsequently,
PI3K overexpression
activated Rac1 and increased ROS generation
Beemiller et al., Mol Biol Cell 2010
:
Inhibition of
PI3K resulted in persistently active Cdc42 and
Rac1 , but not Rac2, in stalled phagocytic cups
Desai et al., J Biol Chem 2010
:
Expression of constitutively active
PI3K stimulated translocation of Tiam1 to the membrane,
increased Rac1 activity, and increased wound healing of airway epithelial cells
Binker et al., Biochem Biophys Res Commun 2010
(Neoplasm Invasiveness...) :
Our results also indicate that signaling events involved in H-R enhanced PANC-1 invasiveness comprehend
PI3K dependent
activation of
Rac1 , which mediated the formation of NADPH generated reactive oxygen species responsible for MMP-2 secretion and activation
Zhang et al., J Cell Mol Med 2011
(Endotoxemia...) :
To determine whether
PI3K regulates
Rac1 activation, cardiomyocytes were treated with LY294002, a PI3K selective inhibitor ... We conclude that
PI3K mediated
Rac1 activation is required for induction of TNF-a expression in cardiomyocytes and cardiac dysfunction during endotoxemia
Venkatesan et al., J Mol Cell Cardiol 2010
:
EMMPRIN activates multiple transcription factors in cardiomyocytes, and induces interleukin-18 expression via
Rac1 dependent
PI3K/Akt/IKK/NF-kappaB andMKK7/JNK/AP-1 signaling ... We show for the first time that EMMPRIN stimulates the activation of NF-kappaB, AP-1, CREB, and ATF-2 in cardiomyocytes, and induces IL-18 expression via
Rac1 dependent
PI3K/Akt/IKK/NF-kappaB and MKK7/JNK/AP-1 signaling
Visser et al., PloS one 2011
:
We used Rac1 dominant negative transfection and chemical inhibition of phosphatidylinositol-3 kinase (PI3K) to show that even though
Rac1 activation was
PI3K dependent , neither was required for Msp induced actin rearrangement
Du et al., PloS one 2011
(Breast Neoplasms) :
Both
PI3K inhibitor LY294002 and ERK inhibitor U0126
suppressed hypoxia induced
Rac1 activation as well as HIF-1a expression ... 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
Song et al., Journal of neuroinflammation 2012
(Neuroblastoma) :
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
Biswas et al., J Biol Chem 2013
:
Only p110ß was necessary for S1P iduced Akt activation, but both
PI3K-C2a and p110ß were
required for
Rac1 activation
Yang et al., Journal of biomedical research 2011
:
Furthermore, expression of dominant negative
Rac1 ( T17N ) could largely
block EGF induced
PI3K/Akt-PAK1 activation and cell migration
Basquin et al., Communicative & integrative biology 2013
:
Our recent work reveals that
PI3K regulates
Rac1 during IL-2R uptake in two ways : via its catalytic activity ( p110 ) and via its regulatory factor ( p85 ) ... Thus,
PI3K regulates both the activation of
Rac1 and its recruitment during IL-2R endocytosis
Keely et al., Nature 1997
(Cell Transformation, Neoplastic...) :
PI(3)K inhibition also disrupts actin structures, suggesting that
activation of
PI(3)K by Cdc42 and
Rac1 alters actin organization, leading to increased motility and invasiveness