Learn More
The pivotal role of kinases in signal transduction and cellular regulation has lent them considerable appeal as pharmacological targets across a broad spectrum of cancers. p21-activated kinases (Paks) are serine/threonine kinases that function as downstream nodes for various oncogenic signalling pathways. Paks are well-known regulators of cytoskeletal(More)
Our previous studies demonstrated that 17beta-estradiol (E2) rapidly induces the interaction of estrogen receptor alpha (ERalpha) with the adapter protein Shc, the translocation of ERalpha to the cell membrane, and the formation of dynamic membrane structures in MCF-7 breast cancer cells. The present study examined how E2 causes ERalpha to translocate to(More)
Lipid peroxidation products can be cytotoxic. Our objectives were (1) to use two pro-oxidants (iron and a pro-oxidative drug) to selectively increase lipid peroxidation in the implanted human breast tumours of mice consuming fish oil and (2) to kill the cancer cells without harming normal host tissues. The theoretical basis for selective cytotoxicity is(More)
Here, we investigated the role of P21-activated kinase 1 (Pak1) signaling in the function of estrogen receptor-alpha (ER-alpha) as assessed by serine 305 (S305) activation and transactivation activity of ER. We found that Pak1 overexpression interfered with the antiestrogenic action of tamoxifen upon the ER transactivation function in hormone-sensitive(More)
PURPOSE Insulin-like growth factor type I receptor (IGF-IR) plays critical roles in epithelial cancer cell development, proliferation, motility, and survival, and new therapeutic agents targeting IGF-IR are in development. Another receptor tyrosine kinase, the epidermal growth factor receptor (EGFR), is an established therapeutic target in head and neck(More)
p21-activated kinase 1 (Pak1) induces cytoskeleton reorganization in part by regulating microtubule dynamics through an elusive mechanism. Using a yeast two-hybrid screen, we identified tubulin cofactor B (TCoB) (a cofactor in the assembly of the alpha/beta-tubulin heterodimers) as an interacting substrate of Pak1. Pak1 directly phosphorylated TCoB in vitro(More)
LIM domain only 4 (LMO4), a member of the LIM-only family of transcriptional coregulatory proteins, consists of two LIM protein-protein interaction domains that enable it to function as a linker protein in multiprotein complexes. Here, we have identified estrogen receptor alpha (ERalpha) and its corepressor, metastasis tumor antigen 1 (MTA1), as two novel(More)
The C-terminal binding protein 1 (CtBP) is a ubiquitous corepressor linking the recruitment of DNA- and histone-modifying proteins to sequence-specific DNA-binding proteins and facilitating gene regulation during development and oncogenesis. We describe here the binding, phosphorylation and functional regulation of CtBP by the p21-activated kinase 1 (Pak1).(More)
Diagnosis of OLTs requires a high index of suspicion because these lesions are rare and the symptoms can be falsely attributed to acute or chronic ankle sprains. When no abnormality is present on plain radiographs, a bone scan or MRI can reliably identify the presence of an OLT. CT scanning can provide even better detail of the location and size of the(More)
Integrin-linked kinase (ILK) is a phosphorylated protein that regulates physiological processes that overlap with those regulated by p21-activated kinase 1 (PAK1). Here we report the possible role of ILK phosphorylation by PAK1 in ILK-mediated signaling and intracellular translocation. We found that PAK1 phosphorylates ILK at threonine-173 and serine-246 in(More)