Genetic and pharmacological analyses of Syk function in alphaIIbbeta3 signaling in platelets - PubMed (original) (raw)
. 1999 Apr 15;93(8):2645-52.
Affiliations
- PMID: 10194444
Free article
Genetic and pharmacological analyses of Syk function in alphaIIbbeta3 signaling in platelets
D A Law et al. Blood. 1999.
Free article
Abstract
Agonists induce inside-out alphaIIbbeta3 signaling resulting in fibrinogen binding and platelet aggregation. These in turn trigger outside-in signaling resulting in further platelet stimulation. Because the Syk tyrosine kinase is activated during both phases of integrin signaling, we evaluated its role in alphaIIbbeta3 function in murine platelets rendered null for Syk by gene targeting and in human platelets incubated with piceatannol, a tyrosine kinase inhibitor reportedly selective for Syk. Both Syk null murine platelets and piceatannol-treated human platelets exhibited a partial, but statistically significant defect in activation of alphaIIbbeta3 by adenine diphosphate (ADP) +/- epinephrine as assessed by fibrinogen binding. Syk null platelets adhered normally to immobilized fibrinogen, and mice with these platelets exhibited normal tail bleeding times. In contrast, piceatannol treatment of human platelets completely inhibited platelet adhesion to immobilized fibrinogen. The discrepancy in extent of integrin dysfunction between murine and human platelet models may be due to lack of specificity of piceatannol, because this compound inhibited the activity of Src and FAK as well as Syk and also reduced tyrosine phosphorylation of multiple platelet proteins. These results provide genetic evidence that Syk plays a role in alphaIIbbeta3 signaling in platelets and pharmacological evidence that, although piceatannol also inhibits alphaIIbbeta3 signaling, it does so by inhibtion of multiple protein tyrosine kinases.
Similar articles
- Coordinate interactions of Csk, Src, and Syk kinases with [alpha]IIb[beta]3 initiate integrin signaling to the cytoskeleton.
Obergfell A, Eto K, Mocsai A, Buensuceso C, Moores SL, Brugge JS, Lowell CA, Shattil SJ. Obergfell A, et al. J Cell Biol. 2002 Apr 15;157(2):265-75. doi: 10.1083/jcb.200112113. Epub 2002 Apr 8. J Cell Biol. 2002. PMID: 11940607 Free PMC article. - Thrombspondin acts via integrin-associated protein to activate the platelet integrin alphaIIbbeta3.
Chung J, Gao AG, Frazier WA. Chung J, et al. J Biol Chem. 1997 Jun 6;272(23):14740-6. doi: 10.1074/jbc.272.23.14740. J Biol Chem. 1997. PMID: 9169439 - Micromolar concentrations of citalopram or escitalopram inhibit glycoprotein VI-mediated and integrin αIIbβ3-mediated signaling in human platelets.
Tseng YL, Braun A, Chang JP, Chiang ML, Tseng CY, Chen W. Tseng YL, et al. Toxicol Appl Pharmacol. 2019 Feb 1;364:106-113. doi: 10.1016/j.taap.2018.12.016. Epub 2018 Dec 25. Toxicol Appl Pharmacol. 2019. PMID: 30592962 - Integrin alpha(IIb)beta(3) signaling in platelet adhesion and aggregation.
Parise LV. Parise LV. Curr Opin Cell Biol. 1999 Oct;11(5):597-601. doi: 10.1016/s0955-0674(99)00018-6. Curr Opin Cell Biol. 1999. PMID: 10508650 Review. - Beta3 tyrosine phosphorylation in alphaIIbbeta3 (platelet membrane GP IIb-IIIa) outside-in integrin signaling.
Phillips DR, Nannizzi-Alaimo L, Prasad KS. Phillips DR, et al. Thromb Haemost. 2001 Jul;86(1):246-58. Thromb Haemost. 2001. PMID: 11487013 Review.
Cited by
- Sinomenium acutum Modulates Platelet Aggregation and Thrombus Formation by Regulating the Glycoprotein VI-Mediated Signalosome in Mice.
Kim YJ, Kim TI, Lee A, Kim K, Hwang YH. Kim YJ, et al. Pharmaceuticals (Basel). 2023 Dec 20;17(1):6. doi: 10.3390/ph17010006. Pharmaceuticals (Basel). 2023. PMID: 38275992 Free PMC article. - TULA-Family Regulators of Platelet Activation.
Kunapuli SP, Tsygankov AY. Kunapuli SP, et al. Int J Mol Sci. 2022 Nov 28;23(23):14910. doi: 10.3390/ijms232314910. Int J Mol Sci. 2022. PMID: 36499237 Free PMC article. Review. - Antithrombotic Effects of Fostamatinib in Combination with Conventional Antiplatelet Drugs.
Harbi MH, Smith CW, Alenazy FO, Nicolson PLR, Tiwari A, Watson SP, Thomas MR. Harbi MH, et al. Int J Mol Sci. 2022 Jun 23;23(13):6982. doi: 10.3390/ijms23136982. Int J Mol Sci. 2022. PMID: 35805988 Free PMC article. - Galectin 3 enhances platelet aggregation and thrombosis via Dectin-1 activation: a translational study.
Chen Y, Fu W, Zheng Y, Yang J, Liu Y, Qi Z, Wu M, Fan Z, Yin K, Chen Y, Gao W, Ding Z, Dong J, Li Q, Zhang S, Hu L. Chen Y, et al. Eur Heart J. 2022 Oct 7;43(37):3556-3574. doi: 10.1093/eurheartj/ehac034. Eur Heart J. 2022. PMID: 35165707 Free PMC article. - Standardization and Validation of Fluorescence-Based Quantitative Assay to Study Human Platelet Adhesion to Extracellular-Matrix in a 384-Well Plate.
Martins Lima A, Saint Auguste DS, Cuenot F, Martins Cavaco AC, Lachkar T, Khawand CME, Fraga-Silva RA, Stergiopulos N. Martins Lima A, et al. Int J Mol Sci. 2020 Sep 7;21(18):6539. doi: 10.3390/ijms21186539. Int J Mol Sci. 2020. PMID: 32906775 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
Miscellaneous