A Calculus of Chemical Systems

In recent years various calculi have been proposed for modelling biological systems, typically intracellular pathways. These calculi generally fall into one of two camps: ones based on process calculi, such as Milner’s pi-calculus [24], and rule-based ones. Examples of the former include [31, 32, 30]; examples of the latter include BIOCHAM, κ, BioNet

Extracellular Signal-regulated Kinase Phosphorylates Tumor Necrosis Factor α-converting Enzyme at Threonine 735: A Potential Role in Regulated Shedding

The ectodomain of certain transmembrane proteins can be released by the action of cell surface proteases, termed secretases. Here we have investigated how mitogen-activated protein kinases (MAPKs) control the shedding of membrane proteins. We show that extracellular signal-regulated kinase (Erk) acts as an intermediate in protein kinase C-regulated TrkA cleavage. We report that the cytosolic tail of the tumor necrosis factor α-converting enzyme (TACE) is phosphorylated by Erk at threonine 735. In addition, we show that Erk and TACE associate. This association is favored by Erk activation and by the presence of threonine 735. In contrast to the Erk route, the p38 MAPK was able to stimulate TrkA cleavage in cells devoid of TACE activity, indicating that other proteases are also involved in TrkA shedding. These results demonstrate that secretases are able to discriminate between the different stimuli that trigger membrane protein ectodomain cleavage and indicate that phosphorylation by MAPKs may regulate the proteolytic function of membrane secretases