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J. Hoppe

Bio: J. Hoppe is an academic researcher from University of Würzburg. The author has contributed to research in topics: Ena/Vasp homology proteins & Vasodilator-stimulated phosphoprotein. The author has an hindex of 2, co-authored 2 publications receiving 669 citations.

Papers
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Journal ArticleDOI
TL;DR: Experiments with 32P-labeled platelets provided evidence that VASP is phosphorylated at the same three identified sites also in intact cells and that selective activation of cAK or cGK primarily increased the phosphorylation of both serine 2 and serine 1 but not threonine.

467 citations

Journal ArticleDOI
TL;DR: The results provide evidence for the structural basis by which VASP, both a target of the cAMP and cGMP signal transduction pathways and a component of the actin‐based cytoskeleton, including the cytos skeleton‐membrane interface, may be able to exchange signals between these networks.
Abstract: The vasodilator-stimulated phosphoprotein (VASP), a substrate for cAMP- and cGMP-dependent protein kinases in vitro and in intact cells, is associated with actin filaments, focal adhesions and dynamic membrane regions. VASP, cloned here from human HL-60 and canine MDCK cells, is organized into three distinct domains. A central proline-rich domain contains a GPPPPP motif as a single copy and as a 3-fold tandem repeat, as well as three conserved phosphorylation sites for cyclic nucleotide-dependent protein kinases. A C-terminal domain contains a repetitive mixed-charge cluster which is predicted to form an alpha-helix. The hydrodynamic properties of purified human VASP together with the calculated molecular mass of cloned VASP suggest that the native protein is a homotetramer with an elongated structure. VASP over-expressed in transiently transfected BHK21 cells was predominantly detected at stress fibres, at focal adhesions and in F-actin-containing cell surface protrusions, whereas truncated VASP lacking the C-terminal domain was no longer concentrated at focal adhesions. These data indicate that the C-terminal domain is required for anchoring VASP at focal adhesion sites, whereas the central domain is suggested to mediate VASP interaction with profilin. Our results provide evidence for the structural basis by which VASP, both a target of the cAMP and cGMP signal transduction pathways and a component of the actin-based cytoskeleton, including the cytoskeleton-membrane interface, may be able to exchange signals between these networks.

220 citations


Cited by
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Journal ArticleDOI
TL;DR: Focal adhesions are sites of tight adhesion to the underlying extracellular matrix developed by cells in culture and are regions of signal transduction that relate to growth control.
Abstract: Focal adhesions are sites of tight adhesion to the underlying extracellular matrix developed by cells in culture. They provided a structural link between the actin cytoskeleton and the extracellular matrix and are regions of signal transduction that relate to growth control. The assembly of focal adhesions is regulated by the GTP-binding protein Rho. Rho stimulates contractility which, in cells that are tightly adherent to the substrate, generates isometric tension. In turn, this leads to the bundling of actin filaments and the aggregation of integrins (extracellular matrix receptors) in the plane of the membrane. The aggregation of integrins activates the focal adhesion kinase and leads to the assembly of a multicomponent signaling complex.

1,950 citations

Journal ArticleDOI
01 Jul 1999-Neuron
TL;DR: It is reported that Shank proteins also bind to Homer, and Shank may cross-link Homer and PSD-95 complexes in the PSD and play a role in the signaling mechanisms of both mGluRs and NMDA receptors.

1,027 citations

Journal ArticleDOI
TL;DR: Current therapies that have successfully targeted the NO-signaling pathway include nitrovasodilators, PDE5 inhibitors, and tadalafil for treatment of a number of vascular diseases including angina pectoris, erectile dysfunction, and pulmonary hypertension, and potential for use of these medications in the treatment of other maladies continues to emerge.
Abstract: To date, studies suggest that biological signaling by nitric oxide (NO) is primarily mediated by cGMP, which is synthesized by NO-activated guanylyl cyclases and broken down by cyclic nucleotide phosphodiesterases (PDEs). Effects of cGMP occur through three main groups of cellular targets: cGMP-dependent protein kinases (PKGs), cGMP-gated cation channels, and PDEs. cGMP binding activates PKG, which phosphorylates serines and threonines on many cellular proteins, frequently resulting in changes in activity or function, subcellular localization, or regulatory features. The proteins that are so modified by PKG commonly regulate calcium homeostasis, calcium sensitivity of cellular proteins, platelet activation and adhesion, smooth muscle contraction, cardiac function, gene expression, feedback of the NO-signaling pathway, and other processes. Current therapies that have successfully targeted the NO-signaling pathway include nitrovasodilators (nitroglycerin), PDE5 inhibitors [sildenafil (Viagra and Revatio), vardenafil (Levitra), and tadalafil (Cialis and Adcirca)] for treatment of a number of vascular diseases including angina pectoris, erectile dysfunction, and pulmonary hypertension; the PDE3 inhibitors [cilostazol (Pletal) and milrinone (Primacor)] are used for treatment of intermittent claudication and acute heart failure, respectively. Potential for use of these medications in the treatment of other maladies continues to emerge.

870 citations

Journal ArticleDOI
01 Oct 1998-Neuron
TL;DR: This work presents evidence that Homer proteins form a physical tether linking mGluRs with the inositol trisphosphate receptors (IP3R), and identifies a novel mechanism in calcium signaling and provides evidence that an IEG, whose expression is driven by synaptic activity, can directly modify a specific synaptic function.

866 citations

Journal ArticleDOI
08 Mar 1996-Cell
TL;DR: WAS provides a novel link between CDC42Hs and the actin cytoskeleton, which suggests a molecular mechanism for many of the cellular abnormalities in WAS.

865 citations