Reactome | FMNL2 binds CDC42:GTP

FMNL2 binds CDC42:GTP

Stable Identifier

R-HSA-5665727

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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FMNL2 binds activated (GTP-bound) CDC42. FMNL2 can be myristoylated on its N-terminal glycine. Although myristoylation is not necessary for the interaction with CDC42, it contributes to FMNL2 activation. Based on the sequence similarity with mouse formin Dia1, binding of CDC42:GTP relieves the autoinhibition of FMNL2 by displacing the C-terminal autoregulatory DAD domain of FMNL2 from the N-terminal FH3 domain (Rose et al. 2005, Lammers et al. 2005). Since formins function as dimers, it is unclear whether the autoinhibitory interaction between FH3 and DAD domain is intramolecular or intermolecular (Xu et al. 2004, Kuhn and Geyer 2014). FMNL2 can also interact with RAC1 in vitro, but it seems that this interaction is not physiologically relevant (Block et al. 2012).

Literature References

PubMed ID	Title	Journal	Year
15864301	Structural and mechanistic insights into the interaction between Rho and mammalian Dia Rose, R, Weyand, M, Lammers, M, Ishizaki, T, Ahmadian, MR, Wittinghofer, A	Nature	2005
15006353	Crystal structures of a Formin Homology-2 domain reveal a tethered dimer architecture Xu, Y, Moseley, JB, Sagot, I, Poy, F, Pellman, D, Goode, BL, Eck, MJ	Cell	2004
24914801	Formins as effector proteins of Rho GTPases Kühn, S, Geyer, M	Small GTPases	2014
22608513	FMNL2 drives actin-based protrusion and migration downstream of Cdc42 Block, J, Breitsprecher, D, Kühn, S, Winterhoff, M, Kage, F, Geffers, R, Duwe, P, Rohn, JL, Baum, B, Brakebusch, C, Geyer, M, Stradal, TE, Faix, J, Rottner, K	Curr. Biol.	2012
16292343	The regulation of mDia1 by autoinhibition and its release by Rho*GTP Lammers, M, Rose, R, Scrima, A, Wittinghofer, A	EMBO J.	2005