Editor-in-Chief: Brüne, Bernhard
Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred
12 Issues per year
IMPACT FACTOR 2015: 2.710
Rank 142 out of 289 in category Biochemistry & Molecular Biology in the 2015 Thomson Reuters Journal Citation Report/Science Edition
SCImago Journal Rank (SJR) 2015: 1.607
Source Normalized Impact per Paper (SNIP) 2015: 0.751
Impact per Publication (IPP) 2015: 2.609
Cell responses to exogenous stimuli often result in a rapid decrease of cell surface density of a wide range of diverse regulatory proteins, receptor and adhesion molecules in particular. This decrease may occur in a liganddependent fashion (downregulation), following endocytosis and degradation by lysosomal proteases, or by downmodulation, where molecules are targeted by endoproteases directly on cell surface. These proteases are recruited by transmodulating agents, different from ligand, which act via their own receptors and the related intracellularlygenerated signals. Endoproteolytic activity determines the release of large portions (shedding) of substrate proteins, called ectodomains, which are usually not ligandbound, and therefore represent biologicallyactive molecules. Ectodomain shedding is involved in a number of pathophysiological processes, such as inflammation, cell degeneration and apoptosis, and oncogenesis. Common features of the process, such as the involvement of protein kinase C and of transmembrane metalloproteases, have been identified. In this review, we summarize basic concepts on downmodulation and ectodomain shedding, and provide an update of the issue with respect to: (i) new entries to the list of molecules found involved in the process; (ii) current views about the upstream control of shedding, i.e. the pathways linking the signals triggered by the transmodulating agents to the activation of endoproteolytic activity on the cell surface.
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