Proprotein processing and pancreatic islet function.
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Amino Acid Sequence↗
Biomedical subjects
John Creemers
Publications and source records attributed to John Creemers.
Processing by proprotein convertases is required for glypican-3 modulation of cell survival, Wnt signaling, and gastrulation movements.
Glypican (GPC)-3 inhibits cell proliferation and regulates cell survival during development. This action is demonstrated by GPC3 loss-of-function mutations in humans and mice. Here, we show that the GPC3 core protein is processed by a furinlike convertase. This processing is essential for GPC3 modulating Wnt signaling and cell survival in vitro and for supporting embryonic cell movements in zebrafish. The processed GPC3 core protein is necessary and sufficient for the cell-specific induction of apoptosis, but in vitro effects on canonical and noncanonical Wnt signaling additionally require substitution of the core protein with heparan sulfate. Wnt 5A physically associates only with processed GPC3, and only a form of GPC3 that can be processed by a convertase is able to rescue epiboly and convergence/extension movements in GPC3 morphant embryos. Our data imply that the Simpson-Golabi-Behmel syndrome may in part result from a loss of GPC3 controls on Wnt signaling, and suggest that this function requires the cooperation of both the protein and the heparan sulfate moieties of the proteoglycan.
Animals↗
Proteolytic enzymes as therapeutic targets - Keystone Symposium. 3-8 February 2002, Keystone, CO, USA.
The Keystone Symposium 'Proteolytic Enzymes as Therapeutic Targets' was attended by approximately 150 scientists. Around two-thirds of the participants consisted of representatives from pharmaceutical companies, but representatives from academic institutes dominated the list of speakers. The meeting attracted scientists from many different fields, including biochemistry, molecular biology, structural biology, pharmacology, chemistry, and bioinformatics. The science ranged from the discovery and characterization of novel proteinases to the development and clinical trials of proteinase inhibitors and was presented as posters or in oral sessions. The discussions following the oral presentations were always very animated, but hardly ever heated. Although there were a few new drugs being presented, the real highlight was the enormous potential of recently discovered proteinases as new therapeutic targets. Both pharmaceutical companies and academic institutes are investing in programs to integrate the avalanche of new information coming from functional genomics, proteomics and structural information to create a platform for applied proteinase technology.
Journal Article↗