Novel roles of cAMP/cGMP-dependent signaling in platelets

Journal of Thrombosis and Haemostasis

Volumn 10, Issue 2, 2012, Pages 167-176

  Smolenski, A ^a  

^a UNIVERSITY COLLEGE DUBLIN   (Ireland)

Author keywords

CAMP; CGMP; Kinase; Nitric oxide; Phosphodiesterase; Prostacyclin

Indexed keywords

CYCLIC AMP; CYCLIC AMP DEPENDENT PROTEIN KINASE; CYCLIC GMP; CYCLIC GMP DEPENDENT PROTEIN KINASE; GUANINE NUCLEOTIDE BINDING PROTEIN; PHOSPHODIESTERASE V;

CALCIUM TRANSPORT; HUMAN; NEGATIVE FEEDBACK; NITROSYLATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN PHOSPHORYLATION; PROTEIN SYNTHESIS; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; THROMBOCYTE AGGREGATION; THROMBOCYTE FUNCTION;

ANIMALS; BLOOD PLATELETS; CYCLIC AMP; CYCLIC AMP-DEPENDENT PROTEIN KINASES; CYCLIC GMP; CYCLIC GMP-DEPENDENT PROTEIN KINASES; HUMANS; PHOSPHORIC DIESTER HYDROLASES; PHOSPHORYLATION; PLATELET AGGREGATION INHIBITORS; SIGNAL TRANSDUCTION;

EID: 84856512481     PISSN: 15387933     EISSN: 15387836     Source Type: Journal    
DOI: 10.1111/j.1538-7836.2011.04576.x     Document Type: Review

References (117)

1. Kloeze J. Influence of prostaglandins on platelet adhesiveness and platelet aggregation. In: Bergström S, Samuelsson B, eds. Prostaglandins: Proceedings of the 2nd Nobel Symposium. Stockholm: Almqvist and Wicksell, 1966: 241-52.
2. Marquis NR, Vigdahl RL, Tavormina PA. Platelet aggregation. I. Regulation by cyclic AMP and prostaglandin E1. Biochem Biophys Res Commun 1969; 36: 965-72.
3. Moncada S, Gryglewski R, Bunting S, Vane JR. An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature 1976; 263: 663-5.
4. Mellion BT, Ignarro LJ, Ohlstein EH, Pontecorvo EG, Hyman AL, Kadowitz PJ. Evidence for the inhibitory role of guanosine 3′, 5′-monophosphate in ADP-induced human platelet aggregation in the presence of nitric oxide and related vasodilators. Blood 1981; 57: 946-55.
5. Radomski MW, Palmer RM, Moncada S. Comparative pharmacology of endothelium-derived relaxing factor, nitric oxide and prostacyclin in platelets. Br J Pharmacol 1987; 92: 181-7.
6. Chirkov YY, Horowitz JD. Impaired tissue responsiveness to organic nitrates and nitric oxide: a new therapeutic frontier? Pharmacol Ther 2007; 116: 287-305.
7. van Geet C, Izzi B, Labarque V, Freson K. Human platelet pathology related to defects in the G-protein signaling cascade. J Thromb Haemost 2009; 7 (Suppl. 1): 282-6.
8. Michelson AD. Antiplatelet therapies for the treatment of cardiovascular disease. Nat Rev Drug Discov 2010; 9: 154-69.
9. Shinohara Y, Katayama Y, Uchiyama S, Yamaguchi T, Handa S, Matsuoka K, Ohashi Y, Tanahashi N, Yamamoto H, Genka C, Kitagawa Y, Kusuoka H, Nishimaru K, Tsushima M, Koretsune Y, Sawada T, Hamada C. Cilostazol for prevention of secondary stroke (CSPS 2): an aspirin-controlled, double-blind, randomised non-inferiority trial. Lancet Neurol 2010; 9: 959-68.
10. Stasch JP, Pacher P, Evgenov OV. Soluble guanylate cyclase as an emerging therapeutic target in cardiopulmonary disease. Circulation 2011; 123: 2263-73.
11. Rukoyatkina N, Walter U, Friebe A, Gambaryan S. Differentiation of cGMP-dependent and -independent nitric oxide effects on platelet apoptosis and reactive oxygen species production using platelets lacking soluble guanylyl cyclase. Thromb Haemost 2011; 106: 922-33.
12. Schwarz UR, Walter U, Eigenthaler M. Taming platelets with cyclic nucleotides. Biochem Pharmacol 2001; 62: 1153-61.
13. Dittrich M, Birschmann I, Mietner S, Sickmann A, Walter U, Dandekar T. Platelet protein interactions: map, signaling components, and phosphorylation groundstate. Arterioscler Thromb Vasc Biol 2008; 28: 1326-31.
14. Dutta-Roy AK, Sinha AK. Purification and properties of prostaglandin E1/prostacyclin receptor of human blood platelets. J Biol Chem 1987; 262: 12685-91.
15. Noe L, Di Michele M, Giets E, Thys C, Wittevrongel C, De Vos R, Overbergh L, Waelkens E, Jaeken J, van Geet C, Freson K. Platelet Gs hypofunction and abnormal morphology resulting from a heterozygous RGS2 mutation. J Thromb Haemost 2010; 8: 1594-603.
16. Johnston-Cox HA, Yang D, Ravid K. Physiological implications of adenosine receptor-mediated platelet aggregation. J Cell Physiol 2011; 226: 46-51.
17. Yang D, Chen H, Koupenova M, Carroll SH, Eliades A, Freedman JE, Toselli P, Ravid K. A new role for the A2b adenosine receptor in regulating platelet function. J Thromb Haemost 2010; 8: 817-27.
18. Freson K, Hashimoto H, Thys C, Wittevrongel C, Danloy S, Morita Y, Shintani N, Tomiyama Y, Vermylen J, Hoylaerts MF, Baba A, van Geet C. The pituitary adenylate cyclase-activating polypeptide is a physiological inhibitor of platelet activation. J Clin Invest 2004; 113: 905-12.
19. Jantzen HM, Milstone DS, Gousset L, Conley PB, Mortensen RM. Impaired activation of murine platelets lacking G alpha(i2). J Clin Invest 2001; 108: 477-83.
20. Yang J, Wu J, Jiang H, Mortensen R, Austin S, Manning DR, Woulfe D, Brass LF. Signaling through Gi family members in platelets. Redundancy and specificity in the regulation of adenylyl cyclase and other effectors. J Biol Chem 2002; 277: 46035-42.
21. Friebe A, Koesling D. The function of NO-sensitive guanylyl cyclase: what we can learn from genetic mouse models. Nitric Oxide 2009; 21: 149-56.
22. Gambaryan S, Kobsar A, Hartmann S, Birschmann I, Kuhlencordt PJ, Muller-Esterl W, Lohmann SM, Walter U. NO-synthase-/NO-independent regulation of human and murine platelet soluble guanylyl cyclase activity. J Thromb Haemost 2008; 6: 1376-84.
23. Özüyaman B, Godecke A, Kusters S, Kirchhoff E, Scharf RE, Schrader J. Endothelial nitric oxide synthase plays a minor role in inhibition of arterial thrombus formation. Thromb Haemost 2005; 93: 1161-7.
24. Rowley JW, Oler AJ, Tolley ND, Hunter BN, Low EN, Nix DA, Yost CC, Zimmerman GA, Weyrich AS. Genome-wide RNA-seq analysis of human and mouse platelet transcriptomes. Blood 2011; 118: e101-11.
25. Moore C, Tymvios C, Emerson M. Functional regulation of vascular and platelet activity during thrombosis by nitric oxide and endothelial nitric oxide synthase. Thromb Haemost 2010; 104: 342-9.
26. Dangel O, Mergia E, Karlisch K, Groneberg D, Koesling D, Friebe A. Nitric oxide-sensitive guanylyl cyclase is the only nitric oxide receptor mediating platelet inhibition. J Thromb Haemost 2010; 8: 1343-52.
27. Zhang G, Xiang B, Dong A, Skoda RC, Daugherty A, Smyth SS, Du X, Li Z. Biphasic roles for soluble guanylyl cyclase (sGC) in platelet activation. Blood 2011; 118: 3670-9.
28. Li Z, Xi X, Gu M, Feil R, Ye RD, Eigenthaler M, Hofmann F, Du X. A stimulatory role for cGMP-dependent protein kinase in platelet activation. Cell 2003; 112: 77-86.
29. Riba R, Oberprieler NG, Roberts W, Naseem KM. von Willebrand factor activates endothelial nitric oxide synthase in blood platelets by a glycoprotein Ib-dependent mechanism. J Thromb Haemost 2006; 4: 2636-44.
30. Riba R, Sharifi M, Farndale RW, Naseem KM. Regulation of platelet guanylyl cyclase by collagen: evidence that glycoprotein VI mediates platelet nitric oxide synthesis in response to collagen. Thromb Haemost 2005; 94: 395-403.
31. Stojanovic A, Marjanovic JA, Brovkovych VM, Peng X, Hay N, Skidgel RA, Du X. A phosphoinositide 3-kinase-AKT-nitric oxide-cGMP signaling pathway in stimulating platelet secretion and aggregation. J Biol Chem 2006; 281: 16333-9.
32. Gambaryan S, Kobsar A, Rukoyatkina N, Herterich S, Geiger J, Smolenski A, Lohmann SM, Walter U. Thrombin and collagen induce a feedback inhibitory signaling pathway in platelets involving dissociation of the catalytic subunit of protein kinase A from an NFkappaB-IkappaB complex. J Biol Chem 2010; 285: 18352-63.
33. Marshall SJ, Senis YA, Auger JM, Feil R, Hofmann F, Salmon G, Peterson JT, Burslem F, Watson SP. GPIb-dependent platelet activation is dependent on Src kinases but not MAP kinase or cGMP-dependent kinase. Blood 2004; 103: 2601-9.
34. Yin H, Liu J, Li Z, Berndt MC, Lowell CA, Du X. Src family tyrosine kinase Lyn mediates VWF/GPIb-IX-induced platelet activation via the cGMP signaling pathway. Blood 2008; 112: 1139-46.
35. Yin H, Stojanovic A, Hay N, Du X. The role of Akt in the signaling pathway of the glycoprotein Ib-IX induced platelet activation. Blood 2008; 111: 658-65.
36. Riba R, Patel B, Aburima A, Naseem KM. Globular adiponectin increases cGMP formation in blood platelets independently of nitric oxide. J Thromb Haemost 2008; 6: 2121-31.
37. Russo I, Traversa M, Bonomo K, De Salve A, Mattiello L, Del Mese P, Doronzo G, Cavalot F, Trovati M, Anfossi G. In central obesity, weight loss restores platelet sensitivity to nitric oxide and prostacyclin. Obesity (Silver Spring) 2010; 18: 788-97.
38. Hobbs AJ, Moncada S. Antiplatelet properties of a novel, non-NO-based soluble guanylate cyclase activator, BAY 41-2272. Vascul Pharmacol 2003; 40: 149-54.
39. Mullershausen F, Russwurm M, Friebe A, Koesling D. Inhibition of phosphodiesterase type 5 by the activator of nitric oxide-sensitive guanylyl cyclase BAY 41-2272. Circulation 2004; 109: 1711-13.
40. Haslam RJ, Dickinson NT, Jang EK. Cyclic nucleotides and phosphodiesterases in platelets. Thromb Haemost 1999; 82: 412-23.
41. Dunkern TR, Hatzelmann A. The effect of Sildenafil on human platelet secretory function is controlled by a complex interplay between phosphodiesterases 2, 3 and 5. Cell Signal 2005; 17: 331-9.
42. Feijge MA, Ansink K, Vanschoonbeek K, Heemskerk JW. Control of platelet activation by cyclic AMP turnover and cyclic nucleotide phosphodiesterase type-3. Biochem Pharmacol 2004; 67: 1559-67.
43. Sim DS, Merrill-Skoloff G, Furie BC, Furie B, Flaumenhaft R. Initial accumulation of platelets during arterial thrombus formation in vivo is inhibited by elevation of basal cAMP levels. Blood 2004; 103: 2127-34.
44. Hunter RW, Mackintosh C, Hers I. Protein kinase C-mediated phosphorylation and activation of PDE3A regulate cAMP levels in human platelets. J Biol Chem 2009; 284: 12339-48.
45. Zhang W, Colman RW. Thrombin regulates intracellular cyclic AMP concentration in human platelets through phosphorylation/activation of phosphodiesterase 3A. Blood 2007; 110: 1475-82.
46. Macphee CH, Reifsnyder DH, Moore TA, Lerea KM, Beavo JA. Phosphorylation results in activation of a cAMP phosphodiesterase in human platelets. J Biol Chem 1988; 263: 10353-8.
47. Jensen BO, Selheim F, Doskeland SO, Gear AR, Holmsen H. Protein kinase A mediates inhibition of the thrombin-induced platelet shape change by nitric oxide. Blood 2004; 104: 2775-82.
48. Müllershausen F, Friebe A, Feil R, Thompson WJ, Hofmann F, Koesling D. Direct activation of PDE5 by cGMP: long-term effects within NO/cGMP signaling. J Cell Biol 2003; 160: 719-27.
49. Wilson LS, Elbatarny HS, Crawley SW, Bennett BM, Maurice DH. Compartmentation and compartment-specific regulation of PDE5 by protein kinase G allows selective cGMP-mediated regulation of platelet functions. Proc Natl Acad Sci USA 2008; 105: 13650-5.
50. Eigenthaler M, Nolte C, Halbrugge M, Walter U. Concentration and regulation of cyclic nucleotides, cyclic-nucleotide-dependent protein kinases and one of their major substrates in human platelets. Estimating the rate of cAMP-regulated and cGMP-regulated protein phosphorylation in intact cells. Eur J Biochem 1992; 205: 471-81.
51. Nagalla S, Shaw C, Kong X, Kondkar AA, Edelstein LC, Ma L, Chen J, McKnight GS, Lopez JA, Yang L, Jin Y, Bray MS, Leal SM, Dong JF, Bray PF. Platelet microRNA-mRNA coexpression profiles correlate with platelet reactivity. Blood 2011; 117: 5189-97.
52. Francis SH, Poteet-Smith C, Busch JL, Richie-Jannetta R, Corbin JD. Mechanisms of autoinhibition in cyclic nucleotide-dependent protein kinases. Front Biosci 2002; 7: d580-92.
53. Hofmann F. The biology of cyclic GMP-dependent protein kinases. J Biol Chem 2005; 280: 1-4.
54. Lohmann SM, Walter U. Tracking functions of cGMP-dependent protein kinases (cGK). Front Biosci 2005; 10: 1313-28.
55. Massberg S, Sausbier M, Klatt P, Bauer M, Pfeifer A, Siess W, Fassler R, Ruth P, Krombach F, Hofmann F. Increased adhesion and aggregation of platelets lacking cyclic guanosine 3′, 5′-monophosphate kinase I. J Exp Med 1999; 189: 1255-64.
56. Eigenthaler M, Ullrich H, Geiger J, Horstrup K, Honig-Liedl P, Wiebecke D, Walter U. Defective nitrovasodilator-stimulated protein phosphorylation and calcium regulation in cGMP-dependent protein kinase-deficient human platelets of chronic myelocytic leukemia. J Biol Chem 1993; 268: 13526-31.
57. Gambaryan S, Geiger J, Schwarz UR, Butt E, Begonja A, Obergfell A, Walter U. Potent inhibition of human platelets by cGMP analogs independent of cGMP-dependent protein kinase. Blood 2004; 103: 2593-600.
58. Li Z, Zhang G, Feil R, Han J, Du X. Sequential activation of p38 and ERK pathways by cGMP-dependent protein kinase leading to activation of the platelet integrin alphaIIb beta3. Blood 2006; 107: 965-72.
59. Begonja AJ, Geiger J, Rukoyatkina N, Rauchfuss S, Gambaryan S, Walter U. Thrombin stimulation of p38 MAP kinase in human platelets is mediated by ADP and thromboxane A2 and inhibited by cGMP/cGMP-dependent protein kinase. Blood 2007; 109: 616-18.
60. Jackson EC, McNicol A. Cyclic nucleotides inhibit MAP kinase activity in low-dose collagen-stimulated platelets. Thromb Res 2010; 125: 147-51.
61. Blackmore PF. Biphasic effects of nitric oxide on calcium influx in human platelets. Thromb Res 2011; 127: e8-14.
62. Bilodeau ML, Hamm HE. Regulation of protease-activated receptor (PAR) 1 and PAR4 signaling in human platelets by compartmentalized cyclic nucleotide actions. J Pharmacol Exp Ther 2007; 322: 778-88.
63. Margarucci L, Roest M, Preisinger C, Bleijerveld OB, van Holten TC, Heck AJ, Scholten A. Collagen stimulation of platelets induces a rapid spatial response of cAMP and cGMP signaling scaffolds. Mol Biosyst 2011; 7: 2311-19.
64. Antl M, von Bruhl ML, Eiglsperger C, Werner M, Konrad I, Kocher T, Wilm M, Hofmann F, Massberg S, Schlossmann J. IRAG mediates NO/cGMP-dependent inhibition of platelet aggregation and thrombus formation. Blood 2007; 109: 552-9.
65. Lapetina EG, Lacal JC, Reep BR, Molina y Vedia L. A ras-related protein is phosphorylated and translocated by agonists that increase cAMP levels in human platelets. Proc Natl Acad Sci USA 1989; 86: 3131-4.
66. Altschuler D, Lapetina EG. Mutational analysis of the cAMP-dependent protein kinase-mediated phosphorylation site of Rap1b. J Biol Chem 1993; 268: 7527-31.
67. Chrzanowska-Wodnicka M, Smyth SS, Schoenwaelder SM, Fischer TH, White GC II. Rap1b is required for normal platelet function and hemostasis in mice. J Clin Invest 2005; 115: 680-7.
68. Kawata M, Kikuchi A, Hoshijima M, Yamamoto K, Hashimoto E, Yamamura H, Takai Y. Phosphorylation of smg p21, a ras p21-like GTP-binding protein, by cyclic AMP-dependent protein kinase in a cell-free system and in response to prostaglandin E1 in intact human platelets. J Biol Chem 1989; 264: 15688-95.
69. Hata Y, Kaibuchi K, Kawamura S, Hiroyoshi M, Shirataki H, Takai Y. Enhancement of the actions of smg p21 GDP/GTP exchange protein by the protein kinase A-catalyzed phosphorylation of smg p21. J Biol Chem 1991; 266: 6571-7.
70. 2+-mediated activation of Rap1 in human platelets. EMBO J 1997; 16: 252-9.
71. Danielewski O, Schultess J, Smolenski A. The NO/cGMP pathway inhibits Rap 1 activation in human platelets via cGMP-dependent protein kinase I. Thromb Haemost 2005; 93: 319-25.
72. Schultess J, Danielewski O, Smolenski AP. Rap1GAP2 is a new GTPase-activating protein of Rap1 expressed in human platelets. Blood 2005; 105: 3185-92.
73. Hoffmeister M, Riha P, Neumüller O, Danielewski O, Schultess J, Smolenski AP. Cyclic nucleotide-dependent protein kinases inhibit binding of 14-3-3 to the GTPase-activating protein Rap1GAP2 in platelets. J Biol Chem 2008; 283: 2297-306.
74. Tzivion G, Avruch J. 14-3-3 proteins: active cofactors in cellular regulation by serine/threonine phosphorylation. J Biol Chem 2002; 277: 3061-4.
75. Mangin PH, Receveur N, Wurtz V, David T, Gachet C, Lanza F. Identification of five novel 14-3-3 isoforms interacting with the GPIb-IX complex in platelets. J Thromb Haemost 2009; 7: 1550-5.
76. Stefanini L, Bergmeier W. CalDAG-GEFI and platelet activation. Platelets 2010; 21: 239-43.
77. Greco F, Sinigaglia F, Balduini C, Torti M. Activation of the small GTPase Rap2B in agonist-stimulated human platelets. J Thromb Haemost 2004; 2: 2223-30.
78. Gratacap MP, Payrastre B, Nieswandt B, Offermanns S. Differential regulation of Rho and Rac through heterotrimeric G-proteins and cyclic nucleotides. J Biol Chem 2001; 276: 47906-13.
79. Manganello JM, Djellas Y, Borg C, Antonakis K, Le Breton GC. Cyclic AMP-dependent phosphorylation of thromboxane A(2) receptor-associated Galpha(13). J Biol Chem 1999; 274: 28003-10.
80. Manganello JM, Huang JS, Kozasa T, Voyno-Yasenetskaya TA, Le Breton GC. Protein kinase A-mediated phosphorylation of the Galpha13 switch I region alters the Galphabetagamma13-G protein-coupled receptor complex and inhibits Rho activation. J Biol Chem 2003; 278: 124-30.
81. Mazzucato M, Pradella P, Cozzi MR, De Marco L, Ruggeri ZM. Sequential cytoplasmic calcium signals in a 2-stage platelet activation process induced by the glycoprotein Ibalpha mechanoreceptor. Blood 2002; 100: 2793-800.
82. 2+ release in intact rat megakaryocytes via cGMP- and cAMP-dependent protein kinases. J Physiol 1998; 512 (Pt 1): 89-96.
83. El-Daher SS, Patel Y, Siddiqua A, Hassock S, Edmunds S, Maddison B, Patel G, Goulding D, Lupu F, Wojcikiewicz RJ, Authi KS. Distinct localization and function of (1, 4, 5)IP(3) receptor subtypes and the (1, 3, 4, 5)IP(4) receptor GAP1(IP4BP) in highly purified human platelet membranes. Blood 2000; 95: 3412-22.
84. Schinner E, Salb K, Schlossmann J. Signaling via IRAG is essential for NO/cGMP-dependent inhibition of platelet activation. Platelets 2011; 22: 217-27.
85. Hassock SR, Zhu MX, Trost C, Flockerzi V, Authi KS. Expression and role of TRPC proteins in human platelets: evidence that TRPC6 forms the store-independent calcium entry channel. Blood 2002; 100: 2801-11.
86. 2+ store depletion induces the formation of macromolecular complexes involving hTRPC1, hTRPC6, the type II IP3 receptor and SERCA3 in human platelets. Biochim Biophys Acta 2008; 1783: 1163-76.
87. Wardell MR, Reynolds CC, Berndt MC, Wallace RW, Fox JE. Platelet glycoprotein Ib beta is phosphorylated on serine 166 by cyclic AMP-dependent protein kinase. J Biol Chem 1989; 264: 15656-61.
88. Bodnar RJ, Xi X, Li Z, Berndt MC, Du X. Regulation of glycoprotein Ib-IX-von Willebrand factor interaction by cAMP-dependent protein kinase-mediated phosphorylation at Ser 166 of glycoprotein Ib(beta). J Biol Chem 2002; 277: 47080-7.
89. Perrault C, Mangin P, Santer M, Baas MJ, Moog S, Cranmer SL, Pikovski I, Williamson D, Jackson SP, Cazenave JP, Lanza F. Role of the intracellular domains of GPIb in controlling the adhesive properties of the platelet GPIb/V/IX complex. Blood 2003; 101: 3477-84.
90. Andrews RK, Harris SJ, McNally T, Berndt MC. Binding of purified 14-3-3 zeta signaling protein to discrete amino acid sequences within the cytoplasmic domain of the platelet membrane glycoprotein Ib-IX-V complex. Biochemistry 1998; 37: 638-47.
91. Dai K, Bodnar R, Berndt MC, Du X. A critical role for 14-3-3zeta protein in regulating the VWF binding function of platelet glycoprotein Ib-IX and its therapeutic implications. Blood 2005; 106: 1975-81.
92. Roberts W, Michno A, Aburima A, Naseem KM. Nitric oxide inhibits von Willebrand factor-mediated platelet adhesion and spreading through regulation of integrin alpha(IIb)beta(3) and myosin light chain. J Thromb Haemost 2009; 7: 2106-15.
93. Habib A, FitzGerald GA, Maclouf J. Phosphorylation of the thromboxane receptor alpha, the predominant isoform expressed in human platelets. J Biol Chem 1999; 274: 2645-51.
94. Zahedi RP, Lewandrowski U, Wiesner J, Wortelkamp S, Moebius J, Schutz C, Walter U, Gambaryan S, Sickmann A. Phosphoproteome of resting human platelets. J Proteome Res 2008; 7: 526-34.
95. Halbrugge M, Walter U. Purification of a vasodilator-regulated phosphoprotein from human platelets. Eur J Biochem 1989; 185: 41-50.
96. Butt E, Abel K, Krieger M, Palm D, Hoppe V, Hoppe J, Walter U. 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 1994; 269: 14509-17.
97. Smolenski A, Bachmann C, Reinhard K, Honig-Liedl P, Jarchau T, Hoschuetzky H, Walter U. Analysis and regulation of vasodilator-stimulated phosphoprotein serine 239 phosphorylation in vitro and in intact cells using a phosphospecific monoclonal antibody. J Biol Chem 1998; 273: 20029-35.
98. Schäfer A, Burkhardt M, Vollkommer T, Bauersachs J, Münzel T, Walter U, Smolenski A. Endothelium-dependent and -independent relaxation and VASP serines 157/239 phosphorylation by cyclic nucleotide-elevating vasodilators in rat aorta. Biochem Pharmacol 2003; 65: 397-405.
99. Schwarz UR, Geiger J, Walter U, Eigenthaler M. Flow cytometry analysis of intracellular VASP phosphorylation for the assessment of activating and inhibitory signal transduction pathways in human platelets - definition and detection of ticlopidine/clopidogrel effects. Thromb Haemost 1999; 82: 1145-52.
100. Hauser W, Knobeloch KP, Eigenthaler M, Gambaryan S, Krenn V, Geiger J, Glazova M, Rohde E, Horak I, Walter U, Zimmer M. Megakaryocyte hyperplasia and enhanced agonist-induced platelet activation in vasodilator-stimulated phosphoprotein knockout mice. Proc Natl Acad Sci USA 1999; 96: 8120-5.
101. Massberg S, Gruner S, Konrad I, Garcia Arguinzonis MI, Eigenthaler M, Hemler K, Kersting J, Schulz C, Muller I, Besta F, Nieswandt B, Heinzmann U, Walter U, Gawaz M. Enhanced in vivo platelet adhesion in vasodilator-stimulated phosphoprotein (VASP)-deficient mice. Blood 2004; 103: 136-42.
102. Aszodi A, Pfeifer A, Ahmad M, Glauner M, Zhou XH, Ny L, Andersson KE, Kehrel B, Offermanns S, Fassler R. The vasodilator-stimulated phosphoprotein (VASP) is involved in cGMP- and cAMP-mediated inhibition of agonist-induced platelet aggregation, but is dispensable for smooth muscle function. EMBO J 1999; 18: 37-48.
103. Harbeck B, Huttelmaier S, Schluter K, Jockusch BM, Illenberger S. Phosphorylation of the vasodilator-stimulated phosphoprotein regulates its interaction with actin. J Biol Chem 2000; 275: 30817-25.
104. Smolenski A, Poller W, Walter U, Lohmann SM. Regulation of human endothelial cell focal adhesion sites and migration by cGMP-dependent protein kinase I. J Biol Chem 2000; 275: 25723-32.
105. Galler AB, Garcia Arguinzonis MI, Baumgartner W, Kuhn M, Smolenski A, Simm A, Reinhard M. VASP-dependent regulation of actin cytoskeleton rigidity, cell adhesion, and detachment. Histochem Cell Biol 2006; 125: 457-74.
106. Worth DC, Hodivala-Dilke K, Robinson SD, King SJ, Morton PE, Gertler FB, Humphries MJ, Parsons M. Alpha v beta3 integrin spatially regulates VASP and RIAM to control adhesion dynamics and migration. J Cell Biol 2010; 189: 369-83.
107. Butt E, Gambaryan S, Gottfert N, Galler A, Marcus K, Meyer HE. Actin binding of human LIM and SH3 protein is regulated by cGMP- and cAMP-dependent protein kinase phosphorylation on serine 146. J Biol Chem 2003; 278: 15601-7.
108. Traenka J, Hauck CR, Lewandrowski U, Sickmann A, Gambaryan S, Thalheimer P, Butt E. Integrin-dependent translocation of LASP-1 to the cytoskeleton of activated platelets correlates with LASP-1 phosphorylation at tyrosine 171 by Src-kinase. Thromb Haemost 2009; 102: 520-8.
109. Butt E, Immler D, Meyer HE, Kotlyarov A, Laass K, Gaestel M. Heat shock protein 27 is a substrate of cGMP-dependent protein kinase in intact human platelets: phosphorylation-induced actin polymerization caused by HSP27 mutants. J Biol Chem 2001; 276: 7108-13.
110. Kato H, Takai S, Matsushima-Nishiwaki R, Adachi S, Minamitani C, Otsuka T, Tokuda H, Akamatsu S, Doi T, Ogura S, Kozawa O. HSP27 phosphorylation is correlated with ADP-induced platelet granule secretion. Arch Biochem Biophys 2008; 475: 80-6.
111. Chen M, Stracher A. In situ phosphorylation of platelet actin-binding protein by cAMP-dependent protein kinase stabilizes it against proteolysis by calpain. J Biol Chem 1989; 264: 14282-9.
112. Jay D, Garcia EJ, Lara JE, Medina MA, de la Luz Ibarra M. Determination of a cAMP-dependent protein kinase phosphorylation site in the C-terminal region of human endothelial actin-binding protein. Arch Biochem Biophys 2000; 377: 80-4.
113. Cranmer SL, Ashworth KJ, Yao Y, Berndt MC, Ruggeri ZM, Andrews RK, Jackson SP. High shear-dependent loss of membrane integrity and defective platelet adhesion following disruption of the GPIbalpha-filamin interaction. Blood 2011; 117: 2718-27.
114. Hettasch JM, Sellers JR. Caldesmon phosphorylation in intact human platelets by cAMP-dependent protein kinase and protein kinase C. J Biol Chem 1991; 266: 11876-81.
115. Nishikawa M, de Lanerolle P, Lincoln TM, Adelstein RS. Phosphorylation of mammalian myosin light chain kinases by the catalytic subunit of cyclic AMP-dependent protein kinase and by cyclic GMP-dependent protein kinase. J Biol Chem 1984; 259: 8429-36.
116. Isenberg JS, Romeo MJ, Yu C, Yu CK, Nghiem K, Monsale J, Rick ME, Wink DA, Frazier WA, Roberts DD. Thrombospondin-1 stimulates platelet aggregation by blocking the antithrombotic activity of nitric oxide/cGMP signaling. Blood 2008; 111: 613-23.
117. Roberts W, Magwenzi S, Aburima A, Naseem KM. Thrombospondin-1 induces platelet activation through CD36-dependent inhibition of the cAMP/protein kinase A signaling cascade. Blood 2010; 116: 4297-306.