e_re777( EMT ):
RAC1 modulates cytoskeleton remodeling by activating ARFP2 and PIP5K1
ARFP2 functions as an important regulatory element in orchestrating cytoskeletal rearrangements at the cell periphery induced by ARF6 and Rac1
e_re782( EMT ):
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.
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.
In compartment: Nucleus
Participates in complexes:
Participates in reactions:
As Reactant or Product:
- GTP:RHOA:RhoA_cytoskeletal_effectors*@Cytoplasm → Cytoskeleton remodeling@Nucleus
- GTP:RHOB:RhoB_cytoskeletal_effectors*@Cytoplasm → Cytoskeleton remodeling@Nucleus
- ARFIP2@Cytoplasm → Cytoskeleton remodeling@Nucleus
- PIP5K1*@Cytoplasm → Cytoskeleton remodeling@Nucleus
- EMT@Cytoplasm → Cytoskeleton remodeling@Nucleus
- Actin polymerization@Nucleus → Cytoskeleton remodeling@Nucleus
- CDC42:CDC42EP*@Cytoplasm → Cytoskeleton remodeling@Nucleus