title: Platelet signalling networks: pathway perturbation demonstrates differential sensitivity of ADP secretion and fibrinogen binding.
abstract: Platelet signalling responses to single agonists have been identified previously. However, a model of the total platelet signalling network is still lacking. In order to gain insights into this network, we explored the effects of a range of platelet-function inhibitors in two independent assays of platelet function, namely fibrinogen binding and ADP secretion. In this study, we targeted the intracellular signalling molecules targeted intracellular signalling molecules, Syk and PI3K and targeted intracellular signalling molecules, Syk and PI3K, the prostaglandin synthesis enzyme cyclooxygenase, surface receptors for TxA(2) and ADP (P2Y1 and P2Y12) and the integrin cell adhesion molecule, αIIbβ3. We demonstrate that the platelet responses of fibrinogen binding and secretion can be differentially affected by the individual inhibitors permitting the generation of a model delineating novel regulatory links in the platelet signalling network. Importantly, the model illustrates the interconnections among portions that are traditionally studied as separate modules, promoting a more integrated view of the platelet.
authors: Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors: Federica
authors: F
authors: Lombardi
authors: Ciarán
authors: C
authors: De Chaumont
authors: Denis C
authors: DC
authors: Shields
authors: Niamh
authors: N
authors: Moran
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism*; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010973:Platelet Adhesiveness / Q000502:physiology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D058470:Receptors, Purinergic P2Y / Q000378:metabolism; D058925:Receptors, Purinergic P2Y12 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D000072377:Syk Kinase
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C548576:P2RY12 protein, human; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D058470:Receptors, Purinergic P2Y; D058925:Receptors, Purinergic P2Y12; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase