The Vasodilator-Stimulated Phosphoprotein Is Regulated by Cyclic GMP-Dependent Protein Kinase During Neutrophil Spreading

Lawrence, Donald W.; Pryzwansky, Katherine B.

doi:10.4049/jimmunol.166.9.5550

Cited by 33 publications

(26 citation statements)

References 45 publications

(68 reference statements)

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“…This possibility would be in agreement with the findings of Lambrechts et al (2000) and Harbeck et al, (2000), who showed that fully phosphorylated EVL and VASP bind less efficiently to Factin. The possibility that Ena/VASP phosphorylation plays a role in actin-based processes is supported by the observation that VASP phosphorylation directly correlates with spreading of neutrophils (Lawrence and Pryzwansky, 2001). Moreover, Mena phosphorylation is required for its function as negative regulator of cell motility in fibroblasts (Loureiro et al, 2002).…”

Section: Discussionmentioning

confidence: 63%

Contribution of Ena/VASP Proteins to Intracellular Motility ofListeriaRequires Phosphorylation and Proline-rich Core but Not F-Actin Binding or Multimerization

Geese

Loureiro

Bear

et al. 2002

MBoC

101

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The Listeria model system has been essential for the identification and characterization of key regulators of the actin cytoskeleton such as the Arp2/3 complex and Ena/vasodilator-stimulated phosphoprotein (VASP) proteins. Although the role of Ena/VASP proteins in Listeria motility has been extensively studied, little is known about the contributions of their domains and phosphorylation state to bacterial motility. To address these issues, we have generated a panel of Ena/ VASP mutants and, upon expression in Ena/VASP-deficient cells, evaluated their contribution to Ena/VASP function in Listeria motility. The proline-rich region, the putative G-actin binding site, and the Ser/Thr phosphorylation of Ena/VASP proteins are all required for efficient Listeria motility. Surprisingly, the interaction of Ena/VASP proteins with F-actin and their potential ability to form multimers are both dispensable for their involvement in this process. Our data suggest that Ena/VASP proteins contribute to Listeria motility by regulating both the nucleation and elongation of actin filaments at the bacterial surface.

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Section: Discussionmentioning

confidence: 63%

Contribution of Ena/VASP Proteins to Intracellular Motility ofListeriaRequires Phosphorylation and Proline-rich Core but Not F-Actin Binding or Multimerization

Geese

Loureiro

Bear

et al. 2002

MBoC

101

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“…Furthermore, VASP, a member of the actin-binding protein family Drosophila Enabled/VASP, also plays a key role in cell motility (57). In neutrophils, VASP is phosphorylated by cGKI and colocalizes with F-actin in filopodia and focal adhesions during spreading, a time when cGMP levels are elevated (26). Fibroblasts deficient in mammalian homologue of Drosophila Enabled/VASP move faster than controls (58,59), suggesting that a possible mechanism for the increase in motility of cGKI Ϫ/Ϫ neutrophils is the reduced phosphorylation of VASP by cGKI.…”

Section: Chemotaxismentioning

confidence: 99%

“…For example, granule secretion of human neutrophils stimulated with fMLP or A23187 is associated with elevated cGMP levels and the phosphorylation of vimentin by cGKI (9,10,25). Similarly, during neutrophil adhesion and spreading, cGMP levels are elevated, and vasodilatorstimulated phosphoprotein (VASP), a membrane-associated focal adhesion protein, is phosphorylated by cGKI (26). Furthermore, when neutrophils are stimulated with LPS, p38 MAPK is phosphorylated upon accumulation of cGMP (27).…”

mentioning

confidence: 99%

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Neutrophil Dysfunction in Guanosine 3′,5′-Cyclic Monophosphate-Dependent Protein Kinase I-Deficient Mice

Werner

Godfrey²,

Arnold³

et al. 2005

The Journal of Immunology

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The regulation of neutrophil functions by Type I cGMP-dependent protein kinase (cGKI) was investigated in wild-type (WT) and cGKI-deficient (cGKI−/−) mice. We demonstrate that murine neutrophils expressed cGKIα. Similar to the regulation of Ca2+ by cGKI in other cells, there was a cGMP-dependent decrease in Ca2+ transients in response to C5a in WT, but not cGKI−/− bone marrow neutrophils. In vitro chemotaxis of bone marrow neutrophils to C5a or IL-8 was significantly greater in cGKI−/− than in WT. Enhanced chemotaxis was also observed with cGKI−/− peritoneal exudate neutrophils (PE-N). In vivo chemotaxis with an arachidonic acid-induced inflammatory ear model revealed an increase in both ear weight and myeloperoxidase (MPO) activity in ear punches of cGKI−/− vs WT mice. These changes were attributable to enhanced vascular permeability and increased neutrophil infiltration. The total extractable content of MPO, but not lysozyme, was significantly greater in cGKI−/− than in WT PE-N. Furthermore, the percentage of MPO released in response to fMLP from cGKI−/− (69%) was greater than that from WT PE-N (36%). PMA failed to induce MPO release from PE-N of either genotype. In contrast, fMLP and PMA released equivalent amounts of lysozyme from PE-N. However, the percentage released was less in cGKI−/− (∼60%) than in WT (∼90%) PE-N. Superoxide release (maximum velocity) revealed no genotype differences in responses to PMA or fMLP stimulation. In summary, these results show that cGKIα down-regulates Ca2+ transients and chemotaxis in murine neutrophils. The regulatory influences of cGKIα on the secretagogue responses are complex, depending on the granule subtype.

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“…Lamellipodial dynamics and behaviour are regulated by proteins of the Ena/VASP family, which are key controllers of actin polymerization in diverse cellular processes Coppolino et al, 2001;Jay, 2000;Krause et al, 2000;Laurent et al, 1999;Lawrence and Pryzwansky, 2001;Renfranz and Beckerle, 2002;Vasioukhin and Fuchs, 2001). Lamellipodial protrusion rate is directly correlated with the amount of Ena/VASP proteins within these projections (Rottner et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Modulation of lamellipodial structure and dynamics by NO-dependent phosphorylation of VASP Ser239

Lindsay

Ramsey

Aitchison

et al. 2007

Journal of Cell Science

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The initial step in directed cell movement is lamellipodial protrusion, an action driven by actin polymerization. Enabled/vasodilator-stimulated phosphoprotein (Ena/VASP) family proteins are key regulators of this actin polymerization and can control lamellipodial protrusion rate. Ena/VASP proteins are substrates for modification by cyclic-nucleotide-dependent protein kinases at a number of sites. Phosphorylation of Ser239 of VASP in vitro inhibits its anti-capping and filament-bundling activity but the effects of this modification on lamellipodial structure and function are unknown. To examine the functional effects of this modification in living cells, we studied VASP phosphorylation at Ser239 by nitric oxide (NO) stimulation of cGMP-dependent protein kinase. Using live cell imaging of primary cells transfected with GFP-VASP constructs, we found that NO produced rapid retraction of lamellipodia together with cell rounding that was dependent on guanylate cyclase and type II cGMP-dependent protein kinase. In cells expressing a mutant VASP (Ser239Ala) lacking the site preferentially phosphorylated by this kinase, NO had no effect. Phosphorylation of Ser239 of VASP results in loss of lamellipodial protrusions and cell rounding, and is a powerful means of controlling directed actin polymerization within lamellipodia.

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The Vasodilator-Stimulated Phosphoprotein Is Regulated by Cyclic GMP-Dependent Protein Kinase During Neutrophil Spreading

Cited by 33 publications

References 45 publications

Contribution of Ena/VASP Proteins to Intracellular Motility ofListeriaRequires Phosphorylation and Proline-rich Core but Not F-Actin Binding or Multimerization

Contribution of Ena/VASP Proteins to Intracellular Motility ofListeriaRequires Phosphorylation and Proline-rich Core but Not F-Actin Binding or Multimerization

Neutrophil Dysfunction in Guanosine 3′,5′-Cyclic Monophosphate-Dependent Protein Kinase I-Deficient Mice

Modulation of lamellipodial structure and dynamics by NO-dependent phosphorylation of VASP Ser239

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