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Rational design and characterization of a Rac GTPase-specific small molecule inhibitor.
TLDR
A first-generation small-molecule inhibitor of Rac GTPase targeting Rac activation by GEF, identified by a structure-based virtual screening of compounds that fit into a surface groove of Rac1 known to be critical for GEF specification, is reported. Expand
Genetic variation in selenoprotein S influences inflammatory response
TLDR
A direct mechanistic link between SEPS1 and the production of inflammatory cytokines is provided and it is suggested thatSEPS1 has a role in mediating inflammation. Expand
Direct Interaction of p21-Activated Kinase 4 with PDZ-RhoGEF, a G Protein-linked Rho Guanine Exchange Factor*
TLDR
Evidence is provided that PAK4 can negatively regulate the activation of Rho through a direct protein-protein interaction with G protein-linked Rho GEFs, thus providing a novel potential mechanism for cross-talk among Rho GTPases. Expand
Homo- and hetero-oligomerization of PDZ-RhoGEF, LARG and p115RhoGEF by their C-terminal region regulates their in vivo Rho GEF activity and transforming potential
TLDR
These findings suggest the existence of a novel mechanism controlling the activity of PDZ-RhoGEF, LARG, and p115Rho GEFs, which involves homo- and hetero-oligomerization through their inhibitory C-terminal region. Expand
The transcription factor PDX-1 is post-translationally modified by O-linked N-acetylglucosamine and this modification is correlated with its DNA binding activity and insulin secretion in min6
TLDR
Data suggest that O-GlcNAcylation may be involved in the regulation of PDX-1 DNA binding activity and in glucose-stimulated insulin secretion in beta-cells. Expand
p19Arf-p53 Tumor Suppressor Pathway Regulates Cell Motility by Suppression of Phosphoinositide 3-Kinase and Rac1 GTPase Activities*
TLDR
A functional relationship between an established tumor suppressor pathway and a signaling module that controls actin structure and cell motility is suggested and it is shown that p19Arf and p53 negatively regulate cell migration by suppression of PI 3-kinase and Rac1 activities. Expand
Mechanisms of Guanine Nucleotide Exchange and Rac-mediated Signaling Revealed by a Dominant Negative Trio Mutant*
TLDR
A conserved pair of amino acid residues of the Trio-Rac interaction are identified that are likely to be essential to the GEF catalysis of Rho family GTPases and it is demonstrated that a dominant negative mutant derived from a Rho GTPase regulator constitutes a new generation of specific inhibitors of RHo G TPase signaling pathways. Expand
Genetic loci modulating amyloid-beta levels in a mouse model of Alzheimer's disease
TLDR
Three loci on mouse chromosomes 1, 2, and 7 showing significant or suggestive associations with brain Abeta levels are identified, several of which contain regions syntenic to previous reports of linkage in human AD. Expand
Genetic background regulates beta-amyloid precursor protein processing and beta-amyloid deposition in the mouse.
TLDR
It is demonstrated that APP processing, A beta metabolism and A beta deposition are regulated by genetic background and that analysis of these phenotypes in mice should provide new insights into the factors that regulate AD pathogenesis. Expand
A method to determine the ionization efficiency change of peptides caused by phosphorylation
TLDR
A method to measure the relative ionization efficiencies of peptides using specifically designed unlabeled peptides is introduced and the usefulness of the method is demonstrated by assessing the change in ionization efficiency of four peptides introduced by phosphorylation. Expand
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