Increased Spreading, Rac/p21-activated Kinase (PAK) Activity, and Compromised Cell Motility in Cells Deficient in Vasodilator-stimulated Phosphoprotein (VASP)

Arguinzonis, Maísa I. García; Galler, Annette; Walter, Ulrich; Reinhard, Matthias; Simm, Andreas

doi:10.1074/jbc.m202873200

Cited by 42 publications

(55 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although a major role for VASP in angiogenesis and capillary repair processes has not been established yet, it seems to be critically important for the changes seen in VASP Ϫ/Ϫ mice during experimental crescentic nephritis. In addition, the study of Garcia Arguinzonis et al (37) demonstrated significantly enhanced activation of the Rac/p21-activated kinase pathway in VASP Ϫ/Ϫ cells. It was shown previously that the small GTPase Rac is involved in endothelial morphogenesis and cap- Figure 6.…”

Section: Discussionmentioning

confidence: 99%

Vasodilator-Stimulated Phosphoprotein–Deficient Mice Demonstrate Increased Platelet Activation but Improved Renal Endothelial Preservation and Regeneration in Passive Nephrotoxic Nephritis

Hohenstein

Kasperek

Kobelt

et al. 2005

Journal of the American Society of Nephrology

Self Cite

View full text Add to dashboard Cite

Vasodilator-stimulated phosphoprotein (VASP), an actin cytoskeletal protein, is expressed in various cell types including renal cells. In vitro studies provide evidence for a role of VASP regarding platelet activation, cell adhesion, migration, and capillary formation. The in vivo role of VASP was investigated in experimental inflammatory renal disease. Kidneys of healthy VASP deficient (؊/؊) and wild-type (wt) mice were compared regarding morphology and functional parameters. Passive nephrotoxic nephritis was induced in 28 VASP ؊/؊ and 28 wt mice; kidneys were harvested; and tissues were analyzed by morphometric, immunohistochemical, and electron microscopic techniques on days 3, 7, 14, and 28. The time course of disease in VASP ؊/؊ mice differed substantially and biphasically from that in wt controls. Early on, VASP ؊/؊ mice demonstrated increased platelet influx associated with augmented glomerular and tubulointerstitial inflammation and sclerosis. Whereas renal disease continuously worsened up to day 28 in wt controls, renal disease in VASP ؊/؊ mice hardly progressed after day 3 as assessed by various injury indices. This long-term improvement of renal histology in VASP ؊/؊ compared with wt mice was associated with remarkable capillary preservation/regeneration up to day 28 mediated via an increased proliferative and a reduced apoptotic activity of VASP-negative peritubular endothelial cells. Despite an enhanced injury response early on, VASP ؊/؊ mice are protected from long-term progression of nephrotoxic nephritis, which is associated with improved renal endothelial cell preservation and regeneration.

show abstract

Section: Discussionmentioning

confidence: 99%

Vasodilator-Stimulated Phosphoprotein–Deficient Mice Demonstrate Increased Platelet Activation but Improved Renal Endothelial Preservation and Regeneration in Passive Nephrotoxic Nephritis

Hohenstein

Kasperek

Kobelt

et al. 2005

Journal of the American Society of Nephrology

Self Cite

View full text Add to dashboard Cite

show abstract

“…The integrin binding protein nischarin binds and inhibits Pak (53). Loss of the scaffold protein VASP also activates Pak and Rac causing increases in cell spreading and reduced cell migration and reorientation, although the direct target of VASP has not been established (54,55). In addition, merlin, the product of the gene responsible for neurofibromatosis type 2, binds and inhibits Pak.…”

Section: Discussionmentioning

confidence: 99%

Opposing Roles for Akt1 and Akt2 in Rac/Pak Signaling and Cell Migration

Zhou

Tucker

Bae

et al. 2006

Journal of Biological Chemistry

126

121

View full text Add to dashboard Cite

“…The localisation of Ena/VASP family proteins to the lamellipodium tip is highly correlated with the protrusion rate (Rottner et al, 1999a), but the roles of these proteins are still controversial (Arguinzonis et al, 2002;Bear et al, 2000;Bear et al, 2002;Nakagawa et al, 2001;Rottner et al, 1999a). It remains to be shown whether the interaction of IRSp53 with Mena influences actin polymerisation dynamics, either in vitro or in vivo.…”

Section: Discussionmentioning

confidence: 99%

IRSp53 is colocalised with WAVE2 at the tips of protruding lamellipodia and filopodia independently of Mena

Nakagawa

Miki

Nozumi

et al. 2003

Journal of Cell Science

135

120

View full text Add to dashboard Cite

The insulin receptor tyrosine kinase substrate p53 (IRSp53) links Rac and WAVE2 and has been implicated in lamellipodia protrusion. Recently, however,IRSp53 has been reported to bind to both Cdc42 and Mena to induce filopodia. To shed independent light on IRSp53 function we determined the localisations and dynamics of IRSp53 and WAVE2 in B16 melanoma cells. In cells spread well on a laminin substrate, IRSp53 was localised by antibody labelling at the tips of both lamellipodia and filopodia. The same localisation was observed in living cells with IRSp53 tagged with enhanced green florescence protein(EGFP-IRSp53), but only during protrusion. From the transfection of deletion mutants the N-terminal region of IRSp53, which binds active Rac, was shown to be responsible for its localisation. Although IRSp53 has been reported to regulate filopodia formation with Mena, EGFP-IRSp53 showed the same localisation in MVD7 Ena/VASP (vasodilator stimulated phosphoprotein) family deficient cells. WAVE2 tagged with DsRed1 colocalised with EGFP-IRSp53 at the tips of protruding lamellipodia and filopodia and, in double-transfected cells, the IRSp53 signal in filopodia decreased before that of WAVE2 during retraction. These results suggest an alternative modulatory role for IRSp53 in the extension of both filopodia and lamellipodia, through WAVE2.

show abstract

Increased Spreading, Rac/p21-activated Kinase (PAK) Activity, and Compromised Cell Motility in Cells Deficient in Vasodilator-stimulated Phosphoprotein (VASP)

Cited by 42 publications

References 56 publications

Vasodilator-Stimulated Phosphoprotein–Deficient Mice Demonstrate Increased Platelet Activation but Improved Renal Endothelial Preservation and Regeneration in Passive Nephrotoxic Nephritis

Vasodilator-Stimulated Phosphoprotein–Deficient Mice Demonstrate Increased Platelet Activation but Improved Renal Endothelial Preservation and Regeneration in Passive Nephrotoxic Nephritis

Opposing Roles for Akt1 and Akt2 in Rac/Pak Signaling and Cell Migration

IRSp53 is colocalised with WAVE2 at the tips of protruding lamellipodia and filopodia independently of Mena

Contact Info

Product

Resources

About