The 46/50 kDa phosphoprotein VASP purified from human platelets is a novel protein associated with actin filaments and focal contacts.

Reinhard, Matthias; Halbrügge, Maria; Scheer, Ulrich; Wiegand, Christiane; Jockusch, Brigitte M.; Walter, Ulrich

doi:10.1002/j.1460-2075.1992.tb05264.x

Cited by 350 publications

(285 citation statements)

References 46 publications

(47 reference statements)

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“…6A, Western blot analysis of HMVEC lysates after exposure to glutamate (10 M), a concentration that promotes HMVEC barrier (see Fig. 3A), revealed dominant VASP phosphorylation (phosphorylation of serine at position 157 leads to a marked shift in apparent molecular mass of VASP by SDS-PAGE from 46 to 50 kDa) (28). Similarly, exposure of BMVEC to glutamate (0.1 M), a concentration that increases endothelial permeability (see Fig.…”

Section: Glutamate and Mglur Agonists Alter In Vitro Endothelialmentioning

confidence: 87%

Neutrophil-derived Glutamate Regulates Vascular Endothelial Barrier Function

Collard¹,

Park²,

Montalto³

et al. 2002

Journal of Biological Chemistry

151

125

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Endothelial barrier function is altered by the release of soluble polymorphonuclear leukocyte (PMN)-derived mediators during inflammatory states. However, endogenous pathways to describe such changes are only recently appreciated. Using an in vitro endothelial paracellular permeability model, cell-free supernatants from formylmethionylleucylphenylalanine-stimulated PMNs were observed to significantly alter endothelial permeability. Biophysical and biochemical analysis of PMN supernatants identified PMN-derived glutamate in modulating endothelial permeability. Furthermore, novel expression of metabotropic glutamate receptor 1 (mGluR1), mGluR4, and mGluR5 by human brain and dermal microvascular endothelial cells was demonstrated by reverse transcription-PCR, in situ hybridization, immunofluorescence, and Western blot analysis. Treatment of human brain endothelia with glutamate or selective, mGluR group I or III agonists resulted in a time-dependent loss of phosphorylated vasodilatorstimulated phosphoprotein (VASP) and significantly increased endothelial permeability. Glutamate-induced decreases in brain endothelial barrier function and phosphorylated VASP were significantly attenuated by pretreatment of human brain endothelia with selective mGluR antagonists. These observations were extended to an in vivo hypoxic mouse model in which pretreatment with mGluR antagonists significantly decreased fluorescein isothiocyanate-dextran flux across the blood-brain barrier. We conclude that activated human PMNs release glutamate and that endothelial expression of group I or III mGluRs function to decrease human brain endothelial VASP phosphorylation and barrier function. These results identify a novel pathway by which PMN-derived glutamate may regulate human endothelial barrier function.

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Section: Glutamate and Mglur Agonists Alter In Vitro Endothelialmentioning

confidence: 87%

Neutrophil-derived Glutamate Regulates Vascular Endothelial Barrier Function

Collard¹,

Park²,

Montalto³

et al. 2002

Journal of Biological Chemistry

151

125

View full text Add to dashboard Cite

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“…The N-terminal 110 amino acid residues of Homer proteins share sequence and secondary structure similarity with (a) the Ena/VASP homology domain 1 (EVH1 domain) of the Enabled protein of Drosophila (Ena) (18), (b) the vasodilator-stimulated phosphoprotein (VASP) (19,20), and (c) the Ran-binding protein family (21). All these proteins have been implicated in binding to proline-rich domains of various cytoskeletal proteins.…”

Section: Homer Protein Structurementioning

confidence: 99%

Homer/Vesl Proteins and Their Roles in CNS Neurons

Ehrengruber

Kato

Inokuchi

et al. 2004

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“…This 46-kDa protein, termed VASP (vasodilator-and A kinase-stimulated phosphoprotein), has been shown to be widely expressed and localized to cytoplasmic focal adhesions and stress fibers (54). The human VASP protein was demonstrated to be phosphorylated at three sites to varying extents by both cGK and cAK.…”

Section: Effect Of Cgki␤ Overexpression On Cre-dependent Genementioning

confidence: 99%

Cyclic AMP- and Cyclic GMP-dependent Protein Kinases Differ in Their Regulation of Cyclic AMP Response Element-dependent Gene Transcription

Collins

Uhler

1999

Journal of Biological Chemistry

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The ability of cGMP-dependent protein kinases (cGKs) to activate cAMP response element (CRE)-dependent gene transcription was compared with that of cAMP-dependent protein kinases (cAKs). Although both the type I␤ cGMP-dependent protein kinase (cGKI␤) and the type II cAMP-dependent protein kinase (cAKII) phosphorylated the cytoplasmic substrate VASP (vasodilator-and A kinase-stimulated phosphoprotein) to a similar extent, cyclic nucleotide regulation of CRE-dependent transcription was at least 10-fold higher in cAKII-transfected cells than in cGKI␤-transfected cells. Overexpression of each kinase in mammalian cells resulted in a cytoplasmic localization of the unactivated enzyme. As reported previously, the catalytic (C) subunit of cAKII translocated to the nucleus following activation by 8-bromo-cyclic AMP. However, cGKI␤ did not translocate to the nucleus upon activation by 8-bromocyclic GMP. Replacement of an autophosphorylated serine (Ser 79 ) of cGKI␤ with an aspartic acid resulted in a mutant kinase with constitutive kinase activity in vitro and in vivo. The cGKI␤S79D mutant localized to the cytoplasm and was only a weak activator of CRE-dependent gene transcription. However, an amino-terminal deletion mutant of cGKI␤ was found in the nucleus as well as the cytoplasm and was a strong activator of CRE-dependent gene transcription. These data suggest that the inability of cGKs to translocate to the nucleus is responsible for the differential ability of cAKs and cGKs to activate CRE-dependent gene transcription and that nuclear redistribution of cGKs is not required for NO/ cGMP regulation of gene transcription.The cyclic nucleotides, cAMP and cGMP, are intracellular second messengers mediating the actions of a large number of hormones and neurotransmitters. These cyclic nucleotides act to allosterically regulate the action of a small number of important proteins. Unlike cAMP, which acts mainly through cAMP-dependent protein kinases (cAKs), 1 cGMP is able to activate three classes of proteins: ion channels, phosphodiesterases, and cGMP-dependent protein kinases (cGKs). The cAKs and the cGKs are highly homologous protein kinase families with similar substrate specificities. Phosphorylation of cellular proteins by both families of kinases leads to alterations in calcium mobilization, protein phosphatase activity, ion channel function, gene transcription, smooth muscle contractility, and platelet aggregation (1-4). The cGKs are classified into two types based on their historical order of characterization. The type I enzymes (cGKIs) are highly expressed in lung (5

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The 46/50 kDa phosphoprotein VASP purified from human platelets is a novel protein associated with actin filaments and focal contacts.

Cited by 350 publications

References 46 publications

Neutrophil-derived Glutamate Regulates Vascular Endothelial Barrier Function

Neutrophil-derived Glutamate Regulates Vascular Endothelial Barrier Function

Homer/Vesl Proteins and Their Roles in CNS Neurons

Cyclic AMP- and Cyclic GMP-dependent Protein Kinases Differ in Their Regulation of Cyclic AMP Response Element-dependent Gene Transcription

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