title: Voltage sensitive phosphatases: emerging kinship to protein tyrosine phosphatases from structure-function research.
abstract: The transmembrane protein Ci-VSP from the ascidian Ciona intestinalis was described as first member of a fascinating family of enzymes, the voltage sensitive phosphatases (VSPs). Ci-VSP and its voltage-activated homologs from other species are stimulated by positive membrane potentials and dephosphorylate the head groups of negatively charged phosphoinositide phosphates (PIPs). In doing so, VSPs act as control centers at the cytosolic membrane surface, because they intervene in signaling cascades that are mediated by PIP lipids. The characteristic motif CX5RT/S in the active site classifies VSPs as members of the huge family of cysteine-based protein tyrosine phosphatases (PTPs). Although PTPs have already been well-characterized regarding both, structure and function, their relationship to VSPs has drawn only limited attention so far. Therefore, the intention of this review is to give a short overview about the extensive knowledge about PTPs in relation to the facts known about VSPs. Here, we concentrate on the structural features of the catalytic domain which are similar between both classes of phosphatases and their consequences for the enzymatic function. By discussing results obtained from crystal structures, molecular dynamics simulations, and mutagenesis studies, a possible mechanism for the catalytic cycle of VSPs is presented based on that one proposed for PTPs. In this way, we want to link the knowledge about the catalytic activity of VSPs and PTPs.
authors.affiliation: Department of Neurophysiology, Institute of Physiology and Pathophysiology, Philipps-Universität Marburg Marburg, Germany.
authors.forename: Kirstin
authors.initials: K
authors.lastname: Hobiger
authors.affiliation: Max-Volmer-Laboratory of Biophysical Chemistry, Institute of Chemistry, Technische Universität Berlin Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Friedrich
keywords: Cdc25; acid phosphatase; cysteine-based phosphatase; dual-specific phosphatase; low molecular weight phosphatase; phosphoinositide; phosphoproteins; phosphotyrosine