Agonist Receptors and G proteins as Mediators of Platelet Activation

1993 ◽  
pp. 17-36 ◽  
Author(s):  
Lawrence F. Brass ◽  
James A. Hoxie ◽  
Thomas Kieber-Emmons ◽  
David R. Manning ◽  
Mortimer Poncz ◽  
...  
Keyword(s):  
G Proteins ◽  
Platelet Activation

scholarly journals Role of heterotrimeric G proteins in platelet activation and clot formation in platelets treated with integrin αIIbβ3 inhibitor

Platelets ◽  
2017 ◽  
Vol 29 (3) ◽  
pp. 265-269 ◽  
Author(s):  
Ivan Budnik ◽  
Boris Shenkman ◽  
Hagit Hauschner ◽  
Isaac Zilinsky ◽  
Naphtali Savion
Keyword(s):  
G Proteins ◽  
Platelet Activation ◽  
Clot Formation ◽  
Heterotrimeric G Proteins ◽  
Integrin Αiibβ3

G Proteins and the Early Events of Platelet Activation

1997 ◽  
pp. 179-195 ◽  
Author(s):  
Lawrence F. Brass ◽  
Mortimer Poncz ◽  
David R. Manning
Keyword(s):  
G Proteins ◽  
Platelet Activation

The Role of GTP-Binding Proteins in Platelet Activation

1991 ◽  
Vol 66 (04) ◽  
pp. 393-399 ◽  
Author(s):  
David R Manning ◽  
Lawrence F Brass
Keyword(s):  
Molecular Weight ◽  
G Proteins ◽  
Platelet Activation ◽  
Cell Activation ◽  
Binding Proteins ◽  
Protein Transport ◽  
Low Molecular Weight ◽  
Gtp Binding Proteins ◽  
Gtp Binding

SummaryPlatelet activation begins with the binding of an agonist to the cell surface and culminates in the events of platelet aggregation, secretion and clot formation. Recent studies have identified two large families of GTP-binding proteins in platelets that are thought to participate in the events of platelet activation. The first of these are the G proteins, heterotrimeric proteins which are best known for their ability to mediate the interaction between agonist receptors and intracellular enzymes such as adenylyl cyclase, phospholipase C and phospholipase A2. To date, at least six G proteins have been identified in platelets: Gs, Gz, three variants of Gi and either Gq or G11 (or both). An additional, pertussis toxinresistant G protein, Gq, may also be present. The second group of GTP-binding proteins present in platelets is substantially smaller than the heterotrimeric G proteins, ranging in size from 21 to 28 kDa. At least 15 such low molecular weight GTP-binding proteins have been identified in platelets, many of which are homologous to the products of the ras proto-oncogenes. In cells other than platelets, low molecular weight GTP-binding proteins have been implicated in protein transport, cell activation events and malignant transformation. Their role in platelets is unknown.

scholarly journals Decoding Gq Signaling in Platelets

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 866-866
Author(s):  
Xi Chen ◽  
Shuchi Gupta ◽  
Matthew Cooper ◽  
Daniel Dehelian ◽  
Lawrence F. Brass ◽  
...  
Keyword(s):  
G Protein ◽  
G Proteins ◽  
Platelet Activation ◽  
Conflicts Of Interest ◽  
Shape Change ◽  
Rgs Proteins ◽  
Functional Responses ◽  
Binding Interface ◽  
Computational Alanine Scanning ◽  
Binding Interfaces

Abstract Most platelet agonists work through G protein coupled receptors (GPCRs), activating pathways that involve members of the Gq, Gi, and G12 families of heterotrimeric G proteins. Gq is critical for most functional responses during platelet activation. A defect in Gq expression in patients leads to impaired platelet secretion and aggregation, which is associated with bleeding diathesis. We have previously shown that the Regulators of G protein Signaling (RGS) proteins function as negative regulators for platelet activation by limiting G protein-dependent signaling, but much remains to be learned about the mechanisms by which G proteins can be regulated during platelet activation. Here we took advantage of an RGS-insensitive Gq(G188S) mutant mouse line to decipher the regulatory complex of Gq-dependent signaling in platelets. The G188S mutation disrupts RGS18 and Gq interaction in a way similar to what we have observed in an analogous Gi2(G184S) mutation. However, in contrast to increased platelet activation in Gi2(G184S) expressing platelets, G188S expressing platelets have decreased activation in response to thrombin, TxA2 and ADP, but not to collagen. The hemostatic thrombi formed in G188S mice are significantly reduced with constant embolization as compared with WT controls. Underlying these changes is a decrease in Gq-dependent signaling events, whereas shape change, which is G13-mediated, is unaffected. Our data further reveal that PLCβ3 and GRK2 complex with activated Gq, but not to Gi2. The G188S mutation in Gq not only prevents the binding of RGS proteins to Gq but also impairs the Gq/PLCβ3 interaction, though it does not affect the GRK2 binding to Gq. Instead, there an increase of GRK2 binding to Gq. Finally, the structural analysis shows that PLCβ3 shares a large overlapping binding area with RGS18 to Gq. Computational alanine scanning to predict binding interfaces indicates that the G188S mutation resides in a region important for the binding of both PLC and RGS. The PLC binding interface also overlaps with that of GRK2, which suggests that when PLC is in complex with Gq, it precludes the binding of both RGS proteins and GRK2. In the G188S mutant, however, PLC binding is reduced, which may reduce competition and allow more GRK2 to bind. The binding interfaces of RGS and GRK2 are not predicted to be overlapping, raising the possibility that the two proteins could bind simultaneously to activated WT Gq. Collectively, these observations 1) indicate that the feedback mechanism of Gq inactivation in platelets is different from that of Gi2, 2) reveal, for the first time, that a Gq/PLCβ/RGS/GRK2 signaling node is present in platelets and plays an important role in Gq-dependent signaling during platelet activation, and 3) show that the G188S mutation affect Gq-mediated signaling by disrupting Gq/PLCβ/RGS interaction. Disclosures No relevant conflicts of interest to declare.

The novel steroidal glycoside from the dried bulb of Allium Macrostemon Bunge inhibits platelet activation

2010 ◽  
Vol 34 (8) ◽  
pp. S33-S33
Author(s):  
Wenchao Ou ◽  
Haifeng Chen ◽  
Yun Zhong ◽  
Benrong Liu ◽  
Keji Chen
Keyword(s):  
Platelet Activation ◽  
The Novel ◽  
Steroidal Glycoside ◽  
Allium Macrostemon

In vivo lipid peroxidation and platelet activation in Helicobacter pylori infection

2001 ◽  
Vol 120 (5) ◽  
pp. A670-A670
Author(s):  
M NERI ◽  
G DAVI ◽  
D FESTI ◽  
F LATERZA ◽  
A FALCO ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Helicobacter Pylori ◽  
Platelet Activation ◽  
Helicobacter Pylori Infection
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