Pak1, a serine/threonine kinase that regulates the actin cytoskeleton, is an effector of the Rho family GTPases Cdc42 and Rac1. The crystal structure of Pak1 revealed an autoinhibited dimer that must dissociate upon GTPase binding.

The p21-Activated kinase 1 (PAK1), a member of serine-threonine kinases family, was initially identified as an interactor of the Rho GTPases RAC1 and CDC42, which affect a wide range of processes associated with cell motility, survival, metabolism, ...

PAK1 exists as a dimer prior to activation and functions within a large multi-protein complex. Therefore, if a non-functional (e.g. devoid of kinase activity) PAK1 is introduced into a cell it may successfully compete with the endogenous form for inclusion into such complexes.

Aug 4, 2000 · The complex is a dimer (two autoregulatory fragments and two kinase domains), held together by interaction of the autoregulatory fragments. It is a dimer in solution as well as in our crystals; the single-chain species, PAK1 (70–545) is also dimeric. Intact PAK1 also oligomerizes in cells (M.-C. P., M. L., and B. J. M., unpublished data).

Aug 4, 2000 · The 2.3 A resolution crystal structure of a complex between the N-terminal autoregulatory fragment and the C-terminal kinase domain of PAK1 shows that GTPase binding will trigger a series of conformational changes, beginning with disruption of a PAK1 dimer and ending with rearrangement of the kinase active site into a catalytically competent state.

Autoinhibited PAK1 is a dimer, in the crystal structure, in solution, and in cells (Lei et al., 2000; Parrini et al., 2002).

The crystal structure of Pak1 revealed an autoinhibited dimer that must dissociate upon GTPase binding. We show that Pak1 forms homodimers in vivo and that its dimerization is regulated by the intracellular level of GTP-Cdc42 or GTP-Rac1.

Apr 4, 2019 · The previous dimeric model of un-activated PAK1 began with the observation of an asymmetric dimer (an unusual occurrence) in the crystal structure of the PAK1 K299R KD (residues 248–545) in complex with a truncated portion of the N-terminal auto-inhibitory segment (residues 70–149) [22].

Jan 1, 2002 · Pak1, a serine/threonine kinase that regulates the actin cytoskeleton, is an effector of the Rho family GTPases Cdc42 and Rac1. The crystal structure of Pak1 revealed an autoinhibited dimer that must dissociate upon GTPase binding.

Apr 29, 2016 · Using an ELISA-based screening protocol, we identified naphtho (hydro)quinone-based small molecules that allosterically inhibit PAK activity. These molecules interfere with the interactions between...