Ser239
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Home > Phosphorylation Site Page: > Ser239  -  VASP (human)

Site Information
GAKLRKVsKQEEASG   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 448380

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 41 , 51 ) , electrophoretic mobility shift ( 38 , 41 , 43 ) , immunoprecipitation ( 6 , 18 , 27 ) , mass spectrometry ( 4 , 9 , 10 , 13 , 15 , 24 , 27 , 34 ) , mutation of modification site ( 19 , 21 , 22 , 25 , 27 , 32 , 33 , 42 , 43 , 50 ) , peptide sequencing ( 51 ) , phospho-antibody ( 1 , 2 , 6 , 7 , 8 , 11 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 26 , 28 , 29 , 30 , 31 , 32 , 33 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 43 , 44 , 45 , 46 , 48 , 49 , 50 ) , phosphoamino acid analysis ( 47 , 51 ) , phosphopeptide mapping ( 42 , 51 ) , western blotting ( 1 , 2 , 6 , 8 , 11 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 36 , 37 , 38 , 41 , 42 , 43 , 44 , 47 , 48 , 49 , 50 )
Disease tissue studied:
brain cancer ( 43 ) , glioma ( 43 ) , breast cancer ( 6 , 15 ) , breast adenocarcinoma ( 6 ) , HER2 positive breast cancer ( 4 ) , luminal A breast cancer ( 4 ) , luminal B breast cancer ( 4 ) , breast cancer, surrounding tissue ( 4 ) , breast cancer, triple negative ( 4 , 6 ) , gastric cancer ( 27 ) , gastric carcinoma ( 27 ) , hepatocellular carcinoma, surrounding tissue ( 24 ) , lung cancer ( 10 , 18 ) , non-small cell lung adenocarcinoma ( 10 ) , ovarian cancer ( 9 , 23 ) , Niemann-Pick disease ( 30 )
Relevant cell line - cell type - tissue:
'muscle, smooth' ( 7 ) , 293 (epithelial) [PKG1 (human)] ( 44 ) , 293 (epithelial) ( 1 , 33 , 35 , 37 ) , A2780 (ovarian) ( 23 ) , A549 (pulmonary) ( 18 ) , A7r5 ('muscle, smooth') ( 43 ) , AGS (gastric) ( 27 ) , aorta ( 48 ) , BAEC (endothelial) ( 31 , 37 ) , breast ( 4 ) , C6 (glial) ( 43 ) , COS (fibroblast) ( 37 ) , E.coli (bacterial) ( 11 ) , ECV304 (endothelial) ( 33 ) , endothelial-aorta ( 47 ) , epithelial-'kidney, tubule' ( 32 ) , HCC1937 (breast cell) ( 15 ) , heart ( 8 ) , HEK293T (epithelial) ( 34 , 37 ) , HeLa (cervical) ( 1 , 33 ) , hepatocyte-liver ( 24 ) , HMEC (endothelial) ( 6 , 28 ) , HPAEC (endothelial) ( 36 ) , HUVEC (endothelial) ( 29 , 31 , 33 ) , K562 (erythroid) ( 13 ) , keratinocyte ( 32 ) , leukocyte-blood ( 29 ) , lung ( 10 ) , LX-2 (hepatic stellate) ( 19 ) , MCF-7 (breast cell) ( 15 ) , MDA-MB-231 (breast cell) ( 6 ) , MDA-MB-468 (breast cell) ( 6 ) , MDCKII (epithelial) ( 21 ) , mesangial ( 49 ) , microvessel endothelial ( 8 ) , MKN-28 (gastric) ( 27 ) , neuron-'brain, hippocampus' ( 39 ) , neutrophil-blood ( 22 ) , NHF (fibroblast) ( 30 ) , NPC1 (fibroblast) ( 30 ) , OV2008 (ovarian) ( 23 ) , ovary ( 9 ) , platelet ( 2 ) , platelet-blood ( 17 , 20 , 26 , 28 , 29 , 32 , 38 , 41 , 45 , 46 , 49 , 50 , 51 ) , PLB985 (myeloid) ( 22 ) , PtK2 (epithelial) ( 50 ) , T lymphocyte-blood ( 28 ) , T47D (breast cell) ( 6 ) , vascular smooth muscle cell ('muscle, smooth') [VASP (mouse), homozygous knockout] ( 42 ) , VSMC-aorta ( 40 ) , VSMC-aorta [VASP (mouse), homozygous knockout] ( 25 )

Upstream Regulation
Regulatory protein:
ANPA (human) ( 31 ) , PKG1 (cow) ( 31 ) , PKG1 (human) ( 19 , 36 ) , PKG1 iso2 (human) ( 37 ) , PTEN (human) ( 1 )
Putative in vivo kinases:
PKG1 (human) ( 22 , 27 , 39 , 43 ) , PRKD2 (human) ( 6 )
Kinases, in vitro:
PKACA (cow) ( 50 ) , PKACA (human) ( 51 ) , PKG1 (cow) ( 50 ) , PKG1 (human) ( 14 , 51 )
Treatments:
5_6-DCl-cBIMPS ( 50 ) , 8-Rp-cAMP ( 47 ) , ACh ( 7 ) , ADP ( 29 ) , AELE ( 2 ) , alprostadil ( 26 , 38 , 50 ) , ANP ( 31 , 49 ) , arachidonic_acid ( 2 ) , argimesna ( 29 ) , bacterial infection ( 27 ) , caffeic_acid ( 2 ) , cAMP_analog ( 26 ) , carbon_monoxide ( 28 ) , cGMP_analog ( 19 , 20 , 33 , 36 , 37 , 38 , 39 , 41 , 43 , 44 , 45 , 49 , 50 ) , cholesterol ( 30 ) , colforsin ( 7 , 18 , 26 , 45 , 49 ) , CRP ( 26 ) , DDTC ( 48 ) , DEA-NONOate ( 30 , 46 ) , dipyridamole ( 20 ) , DT-2 ( 23 ) , EGF ( 23 ) , epoprostenol ( 50 ) , fMLP ( 22 ) , GF109203X ( 26 ) , glucose ( 28 ) , glutamic acid ( 39 ) , H-89 ( 26 , 45 , 49 ) , H2O2 ( 29 , 36 ) , H8 ( 44 ) , hyperlipidemia ( 48 ) , IGF-1 ( 26 ) , irbesartan ( 48 ) , KT5720 ( 45 ) , KT5823 ( 27 , 44 , 45 , 49 ) , L-NAME ( 29 , 47 ) , L-NMMA ( 29 ) , linoleic_acid ( 46 ) , low_glucose ( 28 ) , methyl-beta-cyclodextrin ( 30 ) , N-nitro-L-arginine ( 48 ) , nitric_oxide ( 20 , 28 , 32 , 41 ) , nitrolinoleate ( 46 ) , ODQ ( 20 , 23 , 29 , 47 ) , PAR1-activating_peptide ( 26 ) , phenylephrine ( 47 ) , phorbol_ester ( 35 , 38 ) , PKI-(14-22)amide ( 45 ) , PP2 ( 29 ) , PP3 ( 29 ) , ristocetin ( 29 ) , rottlerin ( 27 ) , Rp-8pCPT-cGMPS ( 22 , 47 ) , Rp-cAMPS ( 45 ) , Rp-cGMP ( 41 , 45 ) , rutin ( 2 ) , scutellarin ( 8 ) , SKI-1 ( 23 ) , SNAP ( 45 ) , SNP ( 17 , 20 , 29 , 47 , 48 , 49 , 50 ) , sphingosine_1-phosphate ( 31 ) , SU6656 ( 23 ) , thrombin ( 26 , 38 ) , U46619 ( 26 ) , VEGF ( 31 ) , von_Willebrand_factor ( 29 )

Downstream Regulation
Effects of modification on VASP:
enzymatic activity, induced ( 22 ) , intracellular localization ( 22 , 32 )
Effects of modification on biological processes:
cell adhesion, altered ( 25 ) , cell growth, altered ( 42 ) , cell motility, altered ( 25 , 32 ) , cytoskeletal reorganization ( 21 , 27 , 32 ) , transcription, inhibited ( 43 )

References 

1

Zhang Q, et al. (2021) PTENε suppresses tumor metastasis through regulation of filopodia formation. EMBO J, e105806
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2

Lescano CH, et al. (2021) Rutin present in Alibertia edulis extract acts on human platelet aggregation through inhibition of cyclooxygenase/thromboxane. Food Funct 12, 802-814
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3

Zhang S, et al. (2021) Matrine Impairs Platelet Function and Thrombosis and Inhibits ROS Production. Front Pharmacol 12, 717725
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4

Mertins P, et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534, 55-62
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5

Boeing S, et al. (2016) Multiomic Analysis of the UV-Induced DNA Damage Response. Cell Rep 15, 1597-1610
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6

Döppler H, et al. (2015) The phosphorylation status of VASP at serine 322 can be predictive for aggressiveness of invasive ductal carcinoma. Oncotarget 6, 29740-52
26336132   Curated Info

7

Wu Y, Gunst SJ (2015) Vasodilator-stimulated phosphoprotein (VASP) regulates actin polymerization and contraction in airway smooth muscle by a vinculin-dependent mechanism. J Biol Chem 290, 11403-16
25759389   Curated Info

8

Li L, et al. (2015) Scutellarin's Cardiovascular Endothelium Protective Mechanism: Important Role of PKG-Iα. PLoS One 10, e0139570
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9

Mertins P, et al. (2014) Ischemia in tumors induces early and sustained phosphorylation changes in stress kinase pathways but does not affect global protein levels. Mol Cell Proteomics 13, 1690-704
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10

Schweppe DK, Rigas JR, Gerber SA (2013) Quantitative phosphoproteomic profiling of human non-small cell lung cancer tumors. J Proteomics 91, 286-96
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11

Döppler HR, et al. (2013) Protein kinase D1-mediated phosphorylations regulate vasodilator-stimulated phosphoprotein (VASP) localization and cell migration. J Biol Chem 288, 24382-93
23846685   Curated Info

12

Shiromizu T, et al. (2013) Identification of missing proteins in the neXtProt database and unregistered phosphopeptides in the PhosphoSitePlus database as part of the Chromosome-centric Human Proteome Project. J Proteome Res 12, 2414-21
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13

Zhou H, et al. (2013) Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res 12, 260-71
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14

Wong A, et al. (2012) Cyclic GMP-dependent stimulation of serotonin transport does not involve direct transporter phosphorylation by cGMP-dependent protein kinase. J Biol Chem 287, 36051-8
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15

Klammer M, et al. (2012) Phosphosignature predicts dasatinib response in non-small cell lung cancer. Mol Cell Proteomics 11, 651-68
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16

Beli P, et al. (2012) Proteomic Investigations Reveal a Role for RNA Processing Factor THRAP3 in the DNA Damage Response. Mol Cell 46, 212-25
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17

Gegenbauer K, Elia G, Blanco-Fernandez A, Smolenski A (2012) Regulator of G-protein signaling 18 integrates activating and inhibitory signaling in platelets. Blood 119, 3799-807
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18

Lara R, et al. (2011) An siRNA screen identifies RSK1 as a key modulator of lung cancer metastasis. Oncogene 30, 3513-21
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19

Routray C, et al. (2011) Protein kinase G signaling disrupts Rac1-dependent focal adhesion assembly in liver specific pericytes. Am J Physiol Cell Physiol 301, C66-74
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20

Jensen BO, et al. (2011) Dipyridamole synergizes with nitric oxide to prolong inhibition of thrombin-induced platelet shape change. Platelets 22, 7-18
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21

Jaeger V, et al. (2010) Herpes simplex virus type 1 entry into epithelial MDCKII cells: role of VASP activities. J Gen Virol 91, 2152-7
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22

Deevi RK, et al. (2010) Vasodilator-stimulated phosphoprotein regulates inside-out signaling of beta2 integrins in neutrophils. J Immunol 184, 6575-84
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23

Leung EL, et al. (2010) Protein kinase G type Ialpha activity in human ovarian cancer cells significantly contributes to enhanced Src activation and DNA synthesis/cell proliferation. Mol Cancer Res 8, 578-91
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24

Han G, et al. (2010) Phosphoproteome analysis of human liver tissue by long-gradient nanoflow LC coupled with multiple stage MS analysis. Electrophoresis 31, 1080-9
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25

Defawe OD, et al. (2010) VASP phosphorylation at serine239 regulates the effects of NO on smooth muscle cell invasion and contraction of collagen. J Cell Physiol 222, 230-7
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26

Hunter RW, Mackintosh C, Hers I (2009) Protein Kinase C-mediated Phosphorylation and Activation of PDE3A Regulate cAMP Levels in Human Platelets. J Biol Chem 284, 12339-48
19261611   Curated Info

27

Knauer O, et al. (2008) Differential phosphoproteome profiling reveals a functional role for VASP in Helicobacter pylori-induced cytoskeleton turnover in gastric epithelial cells. Cell Microbiol 10, 2285-96
18637808   Curated Info

28

Li Calzi S, et al. (2008) Carbon monoxide and nitric oxide mediate cytoskeletal reorganization in microvascular cells via vasodilator-stimulated phosphoprotein phosphorylation: evidence for blunted responsiveness in diabetes. Diabetes 57, 2488-94
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29

Gambaryan S, et al. (2008) NO-synthase-/NO-independent regulation of human and murine platelet soluble guanylyl cyclase activity. J Thromb Haemost 6, 1376-84
18485089   Curated Info

30

Miersch S, et al. (2008) Plasma membrane cholesterol content affects nitric oxide diffusion dynamics and signaling. J Biol Chem 283, 18513-21
18445594   Curated Info

31

Chen H, et al. (2008) Atrial natriuretic peptide-initiated cGMP pathways regulate vasodilator-stimulated phosphoprotein phosphorylation and angiogenesis in vascular endothelium. J Biol Chem 283, 4439-47
18079117   Curated Info

32

Lindsay SL, et al. (2007) Modulation of lamellipodial structure and dynamics by NO-dependent phosphorylation of VASP Ser239. J Cell Sci 120, 3011-21
17684063   Curated Info

33

Blume C, et al. (2007) AMP-activated protein kinase impairs endothelial actin cytoskeleton assembly by phosphorylating vasodilator-stimulated phosphoprotein. J Biol Chem 282, 4601-12
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34

Molina H, et al. (2007) Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry. Proc Natl Acad Sci U S A 104, 2199-204
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35

Kwan HY, Huang Y, Yao X (2006) Protein kinase C can inhibit TRPC3 channels indirectly via stimulating protein kinase G. J Cell Physiol 207, 315-21
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36

Moldobaeva A, et al. (2006) Role of protein kinase G in barrier-protective effects of cGMP in human pulmonary artery endothelial cells. Am J Physiol Lung Cell Mol Physiol 290, L919-30
16339778   Curated Info

37

Fryer BH, et al. (2006) cGMP-dependent protein kinase phosphorylates p21-activated kinase (Pak) 1, inhibiting Pak/Nck binding and stimulating Pak/vasodilator-stimulated phosphoprotein association. J Biol Chem 281, 11487-95
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38

Wentworth JK, Pula G, Poole AW (2006) Vasodilator-stimulated phosphoprotein (VASP) is phosphorylated on Ser157 by protein kinase C-dependent and -independent mechanisms in thrombin-stimulated human platelets. Biochem J 393, 555-64
16197368   Curated Info

39

Wang HG, et al. (2005) Presynaptic and postsynaptic roles of NO, cGK, and RhoA in long-lasting potentiation and aggregation of synaptic proteins. Neuron 45, 389-403
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40

Melichar VO, et al. (2004) Reduced cGMP signaling associated with neointimal proliferation and vascular dysfunction in late-stage atherosclerosis. Proc Natl Acad Sci U S A 101, 16671-6
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41

Jensen BO, et al. (2004) Protein kinase A mediates inhibition of the thrombin-induced platelet shape change by nitric oxide. Blood 104, 2775-82
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42

Chen L, et al. (2004) Vasodilator-stimulated phosphoprotein regulates proliferation and growth inhibition by nitric oxide in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 24, 1403-8
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43

Zhuang S, et al. (2004) Vasodilator-stimulated phosphoprotein activation of serum-response element-dependent transcription occurs downstream of RhoA and is inhibited by cGMP-dependent protein kinase phosphorylation. J Biol Chem 279, 10397-407
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44

Kwan HY, Huang Y, Yao X (2004) Regulation of canonical transient receptor potential isoform 3 (TRPC3) channel by protein kinase G. Proc Natl Acad Sci U S A 101, 2625-30
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45

Li Z, Ajdic J, Eigenthaler M, Du X (2003) A predominant role for cAMP-dependent protein kinase in the cGMP-induced phosphorylation of vasodilator-stimulated phosphoprotein and platelet inhibition in humans. Blood 101, 4423-9
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46

Coles B, et al. (2002) Nitrolinoleate inhibits platelet activation by attenuating calcium mobilization and inducing phosphorylation of vasodilator-stimulated phosphoprotein through elevation of cAMP. J Biol Chem 277, 5832-40
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47

Ibarra-Alvarado C, et al. (2002) Phosphorylation of blood vessel vasodilator-stimulated phosphoprotein at serine 239 as a functional biochemical marker of endothelial nitric oxide/cyclic GMP signaling. Mol Pharmacol 61, 312-9
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48

Oelze M, et al. (2000) Vasodilator-stimulated phosphoprotein serine 239 phosphorylation as a sensitive monitor of defective nitric oxide/cGMP signaling and endothelial dysfunction. Circ Res 87, 999-1005
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49

Burkhardt M, et al. (2000) KT5823 inhibits cGMP-dependent protein kinase activity in vitro but not in intact human platelets and rat mesangial cells. J Biol Chem 275, 33536-41
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50

Smolenski A, et al. (1998) Analysis and regulation of vasodilator-stimulated phosphoprotein serine 239 phosphorylation in vitro and in intact cells using a phosphospecific monoclonal antibody. J Biol Chem 273, 20029-35
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51

Butt E, et al. (1994) cAMP- and cGMP-dependent protein kinase phosphorylation sites of the focal adhesion vasodilator-stimulated phosphoprotein (VASP) in vitro and in intact human platelets. J Biol Chem 269, 14509-17
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