Phosphoinositide phosphatases in a network of signalling reactions.

Phosphoinositide phosphatases dephosphorylate the three positions (D-3, 4 and 5) of the inositol ring of the poly-phosphoinositides. They belong to different families of enzymes. The PtdIns(3,4)P(2) 4-phosphatase family, the tumour suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN), SAC1 domain phosphatases and myotubularins belong to the tyrosine protein phosphatases superfamily. They share the presence of a conserved cysteine residue in the consensus CX(5)RT/S. Another family consists of the inositol polyphosphate 5-phosphatase isoenzymes. The importance of these phosphoinositide phosphatases in cell regulation is illustrated by multiple examples of their implications in human diseases such as Lowe syndrome, X-linked myotubular myopathy, cancer, diabetes or bacterial infection.Journal ArticleResearch Support, Non-U.S. Gov'tReviewSCOPUS: re.jinfo:eu-repo/semantics/publishe

The emerging role of ADAM metalloproteinases in immunity

Proteolysis is an irreversible physiological process that can result in the termination or activation of protein function. Many transmembrane proteins that are involved in the cellular communication between immune cells and structural cells-for example, Notch, CD23, CD44, and membrane-anchored cytokines and their receptors-are cleaved by the ADAM (a disintegrin and metalloproteinase) family of enzymes. Here, we review recent insights into the molecular activation, substrate specificity and function of ADAM proteins in the development and regulation of the immune system, with a particular focus on the roles of ADAM10 and ADAM17