Spatial colocalization and functional link of purinosomes with mitochondria.

Purine biosynthetic enzymes organize into dynamic cellular bodies called purinosomes. Little is known about the spatiotemporal control of these structures. Using super-resolution microscopy, we demonstrated that purinosomes colocalized with mitochondria, and these results were supported by isolation of purinosome enzymes with mitochondria.

Transmembrane Protein 184A Is a Receptor Required for Vascular Smooth Muscle Cell Responses to Heparin.

Vascular cell responses to exogenous heparin have been documented to include decreased vascular smooth muscle cell proliferation following decreased ERK pathway signaling. However, the molecular mechanism(s) by which heparin interacts with cells to induce those responses has remained unclear. Previously characterized monoclonal antibodies that block heparin binding to vascular cells have been found to mimic heparin effects.

Purinosome formation as a function of the cell cycle.

The de novo purine biosynthetic pathway relies on six enzymes to catalyze the conversion of phosphoribosylpyrophosphate to inosine 5'-monophosphate. Under purine-depleted conditions, these enzymes form a multienzyme complex known as the purinosome. Previous studies have revealed the spatial organization and importance of the purinosome within mammalian cancer cells.

Quantitative analysis of purine nucleotides indicates that purinosomes increase de novo purine biosynthesis.

Enzymes in the de novo purine biosynthesis pathway are recruited to form a dynamic metabolic complex referred to as the purinosome. Previous studies have demonstrated that purinosome assembly responds to purine levels in culture medium. Purine-depleted medium or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT) treatment stimulates the purinosome assembly in HeLa cells.

Heparin responses in vascular smooth muscle cells involve cGMP-dependent protein kinase (PKG).

Published data provide strong evidence that heparin treatment of proliferating vascular smooth muscle cells results in decreased signaling through the ERK pathway and decreases in cell proliferation. In addition, these changes have been shown to be mimicked by antibodies that block heparin binding to the cell surface. Here, we provide evidence that the activity of protein kinase G is required for these heparin effects.

Heparin treatment of vascular smooth muscle cells results in the synthesis of the dual-specificity phosphatase MKP-1.

The ability of heparin to block proliferation of vascular smooth muscle cells has been well documented. It is clear that heparin treatment can decrease the level of ERK activity in vascular smooth muscle cells that are sensitive to heparin. In this study, the mechanism by which heparin induces decreases in ERK activity was investigated by evaluating the dual specificity phosphatase, MKP-1, in heparin treated cells.