GTP:RAC1

Complex GTP:RAC1 map


Complex composition:

  1. GTP map
  2. RAC1 map




GTP:​RAC1@Cytoplasm

Identifiers
NAME:GTP:RAC1

Maps_Modules
 EMT  map  / EMT_REGULATORS  map
 EMT  map  / CELL_CELL_ADHESIONS  map
 EMT  map  / TIGHT_JUNCTIONS  map
 EMT  map  / CYTOSKELETON_POLARITY  map

References
PMID:12480336
PMID:16212495
Rac1 is a member of the Ras superfamily of small GTPases.
It plays essential role in control of the cell polarity, actin cytoskeleton rearrangements, protein trafficking and directed motility in a wide variety of mammalian cells
PMID:11152757
Rac1 belongs to the Rho supgroup of small GTPases protein family.
This subgroup is involved in cytoskeletal control, regulation of stress fibers formation, focal adhesions, cell growth, membrane trafficking, development.
e_re527( EMT  map ):
PMID:19751508
PMID:22270359
PMID:16940750
-In the absence of Wnt ligands, b-catenin is phosphorylated by CK1 and GSK-3 in the context of a destruction complex with APC and Axin.
Phosphorylated b-catenin is consequently targeted for ubiquitination and degraded.
-In the presence of Wnt lignads, upon ligand binding, DVL1 (dishevelled) recruits the Axin-GSK-3 complex, resulting in the sequential phosphorylation of LRP6 by CK1 and GSK-3.
Phoshorylated LRP6 serves as a docking site for additional Axin-GSK-3 complex, resulting in the disassembly of the destruction complex.
Non phosphorylated and thus stabilized b-catenin translocates to the nucleus where it activates transcription of target genes together with LEF/TCFs
PMID:19020303
When Wnt binds its receptor, Frizzled, beta-catenin is released to translocate from the cytoplasm to the nucleus, where it forms a complex with TCF and/or LEF transcription factors and stimulates cyclin D1 gene transcription
(Beta-catenin/TCF)- mediated cyclin D1 gene transcription is further regulated by active Rac signaling, phosphorylation by protein kinase A (PKA)
PMID:15377999
Rac1-GTP augments nuclear accumulation of b-catenin and physical association of Rac1 with b-catenin and/or TCF-4 may facilitate this process.
This culminates in the amplification of b-catenin signaling activity, resulting in enhanced transcriptional activation of perhaps a specific subset of Wnt target genes important in cancer progression.
e_re761( EMT  map ):
PMID:8805275
PMID:8910277
PMID:9744077
PMID:10023776
PMID:11728826
GTP-bound Rac1 activates PAK1,2,3.
The binding of the active GTP form of Rac1 and the PBD domain of PAK1,2,3 promotes autophosphorylation of PAK1,2,3 and activation of JNK pathway.
e_re765( EMT  map ):
Rac1 activates JNK pathway vai PAK-independent mechanisms involving binding and stimulation of MAP3K (MAP3K10 and MAP3K11)
PMID:8910292
MLK3 overexpression is sufficient to activate JNK po- tently without affecting the phosphorylating activity of MAPK or p38
MLK3 binds the GTP-binding proteins Cdc42 and Rac1 in vivo and that MLK3 mediates activation of MEKK-SEK-JNK kinase cascade by Rac1 and Cdc42
PMID:9427749
MLK2 (MAP3K10) and MLK3 (MAP3K11) interact with the activated (GTP-bound) forms of Rac and Cdc42, with a slight preference for Rac.
When expressed in fibroblasts, MLK2 co-localizes with active, dually phosphorylated JNK to punctate structures along microtubules.
MLK2 and MLK3 interact with members of the KIF3 family of kinesin superfamily motor proteins and with KAP3A, the putative targeting component of KIF3 motor complex
PMID:11713255
Rac1 coordinately activates p70S6K and JNK via MLK3 activation
e_re767( EMT  map ):
PMID:14701795
Activated Rac1 activates ARHGEF14 which is a common activator for CDC2 and RHOA
Co-expression of Dbs with activated Rac1 causes enhanced focus forming activity and elevated levels of GTP-bound RhoA in NIH 3T3 cells, indicating that Dbs is activated by the interaction.
e_re771( EMT  map ):
RAC1 binds directly to PARD6 that activates PRKCZ.
This leads to establishment of the cell polarity and promotes cellular transformation.
PMID:10873802
PARD6 links Rac1 and Cdc42 to PKCzeta signaling and cell transformation.
PMID:10934475
PARD6 binds to Cdc42; Rac1; PARD3; PRKC isoforms.
In vitro, PARD3 acts as a substrate and an inhibitor of PRKC.
PARD3 and PARD6 have a scaffolding function, coordinating the activities of several signalling proteins that are implicated in mammalian cell polarity.
PMID:10954424
PARD6 is a binding partner for the Rho GTPases Cdc42 and Rac1
e_re776( EMT  map ):
RAC1 modulates cytoskeleton remodeling by activating ARFP2 and PIP5K1
PMID:9312003
ARFP2 functions as an important regulatory element in orchestrating cytoskeletal rearrangements at the cell periphery induced by ARF6 and Rac1
e_re778( EMT  map ):
PMID:10679324
Rac-associated PIP 5-kinase as the PIP 5-kinase isoforms alpha and beta.
When added to permeabilized platelets, PIP 5-kinase alpha induced actin filament uncapping and assembly.
PIP 5-kinase alpha is a critical mediator of thrombin- and Rac-dependent actin assembly.
PMID:14681219
PIP5K catalyzes the formation of the phospholipid, phosphatidylinositol 4,5-bisphosphate PIP2
RhoA and Rac1 bind and activate PIP5K.
3 isoforms of type I PIP5K (alpha,beta, and gamma) have been identified
RhoA and Rac1, as well as Cdc42, but not RalA and Rap1A, markedly stimulate PIP2 synthesis by all three PIP5K isoforms expressed in human embryonic kidney 293 cells, both in vitro and in vivo.
RhoA-stimulated PIP2 synthesis by the PIP5K isoforms was mediated by the RhoA effector, Rho kinase.
Stimulation of PIP5K isoforms by Rac1 and Cdc42 was apparently independent of and additive with RhoA- and Rho-kinase
RhoA, and to a lesser extent Rac1, but not Cdc42, interacted in a nucleotide-independent form with all three PIP5K isoforms.
Binding of PIP5K isoforms to GTP-bound, but not GDP-bound, RhoA could be displaced by Rho-kinase, suggesting a direct and constitutive PIP5K-Rho GTPase binding, which, however, does not trigger PIP5K activation.
Synthesis of PIP2 by the three PIP5K isoforms is controlled by RhoA, acting via Rho-kinase, as well as Rac1 and Cdc42, implicating that regulation of PIP2 synthesis has a central position in signaling by these three Rho GTPases.
e_re785( EMT  map ):
PMID:12181570
Rac1 binds to NCKAP1 and CYFIP2 and also promotes NCK1 binding to NCKAP1.
This binding inhibits NCKAP1 and CYFIP2 binding to WASF1 and promotes release of the complex of WASF1 and BRK1, thus activating WASF1.
Activated WASF1 then stimulates ARP2/3 that mediates actin cytoskeletal polymerizatioin
e_re788( EMT  map ):
Rac1 binds to BAIAP2 which in turn associates with WASF2.
This stimulates ARP2/3 and leads to actin cytoskeleal polymerization.
PMID:16702231
WAVE2 (so-called WASF2) activates the ARP2/3 complex for Rac-induced actin polymerization during lamellipodium formation
PMID:9843499
WASF (WAVE) as regulator of actin reorganization downstream of Rac.
Expressed WAVE induces the formation of actin filament clusters.
WAVE plays a critical role downstream of Rac in regulating the actin cytoskeleton required for mem- brane rufflin
PMID:12054568
WAVE2 serves a functional partner of IRSp53 by regulating its interaction with Rac.
e_re964( EMT  map ):
PMID:11121431
PMID:15157156
PMID:15229651
Nischarin binds preferentially to the cytoplasmic tail of ITGA5 subunit ti inhibit cell migration.
Nischarin is not found in focal adhesion sites.
Once integrins enter into adhesion sites, Nischarin is released, allowing it to bind to the activated PAK1 in order to inactive PAK1..
This binding is enhaced by active Rac1.
The ability of Nischarin to inhibit PAK1 is related to its ability to inhibit cell motility.

Confidence
REF=5 FUNC=0


Modifications:
Participates in complexes:
In compartment: Cytoplasm
  1. GTP:​RAC1@Cytoplasm map

Participates in reactions:
As Reactant or Product:

  1. RAC1@Cytoplasm map map GTP:​RAC1@Cytoplasm map

  2. GDP:​RAC1@Cytoplasm map map GTP:​RAC1@Cytoplasm map
  3. GTP:​RAC1@Cytoplasm map map GDP:​RAC1@Cytoplasm map
  4. GTP:​RAC1@Cytoplasm map map ARHGEF14*@Cytoplasm map
  5. GTP:​RAC1@Cytoplasm map map NCKAP1@Cytoplasm map
  6. GTP:​RAC1@Cytoplasm map map CYFIP2@Cytoplasm map
  7. GTP:​RAC1@Cytoplasm map + NCK1@Cytoplasm map map NCK1:​RAC1@Cytoplasm map
  8. GTP:​RAC1@Cytoplasm map map Membrane spreading@Cytoplasm map
  9. GDP:​RAC1@Cytoplasm map + GTP@Cytoplasm map map GTP:​RAC1@Cytoplasm map + GDP@Cytoplasm map
  10. GTP:​RAC1@Cytoplasm map map EMT@Cytoplasm map
  11. GTP:​RAC1@Cytoplasm map + PLC-_beta_*@Cytoplasm map map s_s_wnc1_s288

As Catalyser:

  1. LEF1_TCF3_4*@Nucleus map + _beta_-Catenin*@Cytoplasm map map LEF1_TCF3_4*:​_beta_-Catenin*@Nucleus map

  2. PAK*@Cytoplasm map map PAK*|​pho|​active@Cytoplasm map
  3. MAP3K7_10_11*@Cytoplasm map map MAP3K7_10_11*@Cytoplasm map
  4. PAR6*@Cytoplasm map map PAR6*@Cytoplasm map
  5. ARFIP2@Cytoplasm map map ARFIP2@Cytoplasm map
  6. PIP5K1*@Cytoplasm map map PIP5K1*@Cytoplasm map
  7. BAIAP2@Cytoplasm map map BAIAP2@Cytoplasm map
  8. PAK1@Cytoplasm map + NISCH@Nucleus map map NISCH:​PAK1@Cytoplasm map

Leave a Reply