Reactome | DOCK180:ELMO exchanges GTP for GDP, activating RAC1

DOCK180:ELMO exchanges GTP for GDP, activating RAC1

Stable Identifier

R-HSA-5218839

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

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DOCK180:ELMO exchanges GTP for GDP, activating RAC1

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RAC1 is activated from inactive GDP-bound state to active GTP-bound form by the GEF activity of DOCK180:ELMO complex. RAC1 signaling facilitates VEGF-stimulated angiogenesis by regulating endothelial cell migration and vascular permeability. RAC1 promotes migration by stimulating actin reorganisation to form membrane ruffles and lamellipodia. RAC1 is also a critical component of endothelial NADPH oxidase promoting reactive oxygen species (ROS) prodcution. Specifically, VEGF acts through RAC1 to stimulate lamellipodia formation at the leading edge of polarized cells for directional migration, or chemotaxis. RAC1 induces vascular permeability in part by disrupting endothelial cell-cell junctions (Soga et al. 2001a, Soga et al. 2001b, Claesson-Welsh & Welsh, 2013).

Literature References

PubMed ID	Title	Journal	Year
12134158	Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex Macara, IG, Walk, SF, Lu, M, Grimsley, C, Madhani, H, Fink, GR, Brugnera, E, Tosello-Trampont, AC, Ravichandran, KS, Haney, L	Nat Cell Biol	2002

Participants

Input

Output

Participates

as an event of

VEGFA-VEGFR2 Pathway (Homo sapiens)

Catalyst Activity

guanyl-nucleotide exchange factor activity of CRK:DOCK180:ELMO1,ELMO2:VEGFA:p-6Y-VEGFR2:p-SHB:p-7Y-PTK2:SRC-1:HSP90:p-12Y-BCAR1,VEGFA:p-6Y-VEGFR2:p-SHB:p-7Y-PTK2:SRC-1:HSP90:p-Y31,Y118-PXN [plasma membrane]

Physical Entity

CRK:DOCK180:ELMO1,ELMO2:VEGFA:p-6Y-VEGFR2:p-SHB:p-7Y-PTK2:SRC-1:HSP90:p-12Y-BCAR1,VEGFA:p-6Y-VEGFR2:p-SHB:p-7Y-PTK2:SRC-1:HSP90:p-Y31,Y118-PXN [plasma membrane] (Homo sapiens)

Activity

guanyl-nucleotide exchange factor activity (GO:0005085)

Orthologous Events

DOCK180:ELMO exchanges GTP for GDP, activating RAC1 (Bos taurus)

DOCK180:ELMO exchanges GTP for GDP, activating RAC1 (Canis familiaris)

DOCK180:ELMO exchanges GTP for GDP, activating RAC1 (Drosophila melanogaster)

DOCK180:ELMO exchanges GTP for GDP, activating RAC1 (Gallus gallus)

DOCK180:ELMO exchanges GTP for GDP, activating RAC1 (Mus musculus)

DOCK180:ELMO exchanges GTP for GDP, activating RAC1 (Rattus norvegicus)

DOCK180:ELMO exchanges GTP for GDP, activating RAC1 (Sus scrofa)