The role of podoplanin inhibitors in controlling oral cancer progression.

Objective: In this article, we review the current studies on the role of podoplanin in oral cancer and the potential application of podoplanin inhibitors as a therapeutic agent for oral cancer.

Design: The narrative review approach was conducted, providing a comprehensive perspective of related literature. Publications addressing podoplanin and its inhibitors in the context of oral cancer were retrieved from PubMed and Scopus databases.

Signalling pathways regulating galactosaminoglycan synthesis and structure in vascular smooth muscle: Implications for lipoprotein binding and atherosclerosis.

Atherosclerosis commences with the trapping of low density lipoproteins (LDLs) in blood vessels by modified proteoglycans (PGs) with hyperelongated glycosaminoglycan (GAG) chains. GAG chain synthesis and growth factor mediated hyperelongation regulates the composition and size of PGs in a manner that would cause low density lipoprotein (LDLs) retention in vessel wall. Galactosaminoglycans are a class of GAGs, commonly observed on PGs.

Flavopiridol Inhibits TGF--Stimulated Biglycan Synthesis by Blocking Linker Region Phosphorylation and Nuclear Translocation of Smad2.

Transforming growth factor- (TGF-) is a pleiotropic growth factor implicated in the development of atherosclerosis for its role in mediating glycosaminoglycan (GAG) chain hyperelongation on the proteoglycan biglycan, a phenomenon that increases the binding of atherogenic lipoproteins in the vessel wall. Phosphorylation of the transcription factor Smad has emerged as a critical step in the signaling pathways that control the synthesis of biglycan, both the core protein and the GAG chains. We have used flavopiridol, a well-known cyclin-dependent kinase inhibitor, to study the role of linker region phosphorylation in the TGF--stimulated synthesis of biglycan.

The role of specific Smad linker region phosphorylation in TGF-β mediated expression of glycosaminoglycan synthesizing enzymes in vascular smooth muscle.

Hyperelongation of glycosaminoglycan chains on proteoglycans facilitates increased lipoprotein binding in the blood vessel wall and the development of atherosclerosis. Increased mRNA expression of glycosaminoglycan chain synthesizing enzymes in vivo is associated with the development of atherosclerosis. In human vascular smooth muscle, transforming growth factor-β (TGF-β) regulates glycosaminoglycan chain hyperelongation via ERK and p38 as well as Smad2 linker region (Smad2L) phosphorylation.

The expansion of GPCR transactivation-dependent signalling to include serine/threonine kinase receptors represents a new cell signalling frontier.

G protein-coupled receptor (GPCR) signalling is mediated through transactivation-independent signalling pathways or the transactivation of protein tyrosine kinase receptors and the recently reported activation of the serine/threonine kinase receptors, most notably the transforming growth factor-β receptor family. Since the original observation of GPCR transactivation of protein tyrosine kinase receptors, there has been considerable work on the mechanism of transactivation and several pathways are prominent. These pathways include the "triple membrane bypass" pathway and the generation of reactive oxygen species.

Peptidyl-prolyl isomerases: functionality and potential therapeutic targets in cardiovascular disease.

Peptidyl-prolyl cis/trans isomerases (PPIases) are a conserved group of enzymes that catalyse the conversion between cis and trans conformations of proline imidic peptide bonds. These enzymes play critical roles in regulatory mechanisms of cellular function and pathophysiology of disease. There are three different classes of PPIases and increasing interest in the development of specific PPIase inhibitors.

Transforming growth factor β-mediated site-specific Smad linker region phosphorylation in vascular endothelial cells.

Objectives: Transforming growth factor (TGF)-β regulates the function of vascular endothelial cells and may be involved in endothelial dysfunction. The canonical TGF-β pathway involves TGF-β receptor-mediated carboxy-terminal phosphorylation of Smad2; however, TGF-β signalling also activates numerous serine/threonine kinases that phosphorylate Smad2 in its linker region. The expression of phosphorylated Smad linker proteins were determined following TGF-β stimulation in the absence and presence of different serine/threonine kinase inhibitors in vascular endothelial cells.

Transforming growth factor-β signalling: role and consequences of Smad linker region phosphorylation.

Transforming growth factor-β (TGF-β) is a secreted homodimeric protein that plays an important role in regulating various cellular responses including cell proliferation and differentiation, extracellular matrix production, embryonic development and apoptosis. Disruption of the TGF-β signalling pathway is associated with diverse disease states including cancer, renal and cardiac fibrosis and atherosclerosis. At the cell surface TGF-β complex consists of two type I and two type II transmembrane receptors (TβRI and TβRII respectively) which have serine/threonine kinase activity.

Suramin inhibits PDGF-stimulated receptor phosphorylation, proteoglycan synthesis and glycosaminoglycan hyperelongation in human vascular smooth muscle cells.

Objectives: Suramin is a polysulfonated naphthylurea with antiparasitic and potential antineoplastic activity. Suramin's pharmacological actions, which have not yet been fully elucidated, include antagonism of the action of platelet-derived growth factor (PDGF) at its receptor. We investigated the effects of suramin on PDGF-stimulated proteoglycan synthesis.