The p21-activated kinase 4-Slug transcription factor axis promotes epithelial-mesenchymal transition and worsens prognosis in prostate cancer.

Epithelial-mesenchymal transition (EMT) facilitates cancer invasion and metastasis and thus accelerates cancer progression. p21-activated kinase 4 (PAK4) is a critical regulator of prostate cancer (PC) progression. Here, we report that PAK4 activation promotes PC progression through the EMT regulator Slug.

Nigral dopaminergic PAK4 prevents neurodegeneration in rat models of Parkinson's disease.

Parkinson's disease (PD) is characterized by progressive loss of dopaminergic (DA) neurons in the substantia nigra. No neuroprotective treatments have successfully prevented the progression of this disease. We report that p21-activated kinase 4 (PAK4) is a key survival factor for DA neurons.

Small molecules that allosterically inhibit p21-activated kinase activity by binding to the regulatory p21-binding domain.

p21-activated kinases (PAKs) are key regulators of actin dynamics, cell proliferation and cell survival. Deregulation of PAK activity contributes to the pathogenesis of various human diseases, including cancer and neurological disorders. Using an ELISA-based screening protocol, we identified naphtho(hydro)quinone-based small molecules that allosterically inhibit PAK activity.

Phosphorylation of β-catenin at serine 663 regulates its transcriptional activity.

β-Catenin, a component of Wnt signaling, plays a key role in colorectal carcinogenesis. The phosphorylation status of β-catenin determines its fate and affects its cellular function, and serine 675 (S675) was previously identified as a common target of p21-activated kinase 1 (PAK1) and protein kinase A. In the present study, we explored the PAK1-specific phosphorylation site(s) in β-catenin.

Involvement of betaPIX in angiotensin II-induced migration of vascular smooth muscle cells.

Angiotensin II (Ang II) stimulates migration of vascular smooth muscle cell (VSMC) in addition to its contribution to contraction and hypertrophy. It is well established that Rho GTPases regulate cellular contractility and migration by reorganizing the actin cytoskeleton. Ang II activates Rac1 GTPase, but its upstream guanine nucleotide exchange factor (GEF) remains elusive.

Novel candidate targets of Wnt/beta-catenin signaling in hepatoma cells.

The activity of beta-catenin/TCF, the key component of Wnt signaling pathway, is frequently deregulated in HCC, resulting in the activation of genes whose dysregulation has significant consequences on tumor development. Therefore, identifying the target genes of Wnt signaling is important for understanding beta-catenin-mediated carcinogenesis. We analyzed the transcriptome profile of human hepatoma cell lines using cDNA microarrays representing 15,127 unique, liver-enriched gene loci to identify the target genes of beta-catenin-mediated transcription (p<0.

STMN2 is a novel target of beta-catenin/TCF-mediated transcription in human hepatoma cells.

The activity of beta-catenin/TCF, the key component of Wnt signaling pathway, is frequently deregulated in human cancers, resulting in the activation of genes whose dysregulation has significant consequences on tumor development. Therefore, identifying the target genes of Wnt signaling is important for understanding beta-catenin-mediated carcinogenesis. Here, we report STMN2, a gene implicated in the regulation of microtubule dynamics, as a novel target of beta-catenin-mediated transcription.

Direct binding of recombinant plasminogen kringle 1-3 to angiogenin inhibits angiogenin-induced angiogenesis in the chick embryo CAM.

Angiogenin is one of the most potent angiogenesis-inducing proteins. Angiostatin is one of the most potent angiogenesis inhibitors, and it contains the first four kringle domains of plasminogen (K1-4). Recombinant human plasminogen kringle 1-3 (rK1-3) was expressed in Escherichia coli and purified to homogeneity.