Platelet Activation Flashcards
What is the main platelet receptor?
GPIb/V/IX protein complex
What does GPIb/V/IX need to bind to collagen?
VWF
What are the 5 molecules that make up the GPIb/V/IX complex?
GPIX
Two GPIb beta
GPIb alpha
GPV
Which molecule binds to VWF?
GPIb alpha
What are the 3 main signaling molecules that the GPIb/V/IX complex binds to?
Calmodulin, 14-3-3 and P85
How does the GPIb/V/IX bind to actin on the cytoskeleton?
Via filamin
How do platelets bind directly to collagen after initial attachement?
via glycoprotein VI (tyrosine kinase signaling)
intergrin alpha 2 beta 1 receptors
What is ITAM on GPVI?
Immunoreceptor tyrosine-based activation motif
What is the function of ITAM on GPVI?
Its phosphorylation leads to Src tyrosine kinase recruitment & PLCy2 activation
What is thrombin?
A serine protease involved in fibrin formation & platelet activation
How does thrombin activate platelets?
Cleaves the N terminus off specific G protein coupled receptors unmasking a ligand which binds PAR receptors -> Gq & G12/13 signalling
What are the 2 protease activated receptors?
PAR1
PAR4
What does Gq signalling cause?
Activation of PLC beta which increases Ca2+ levels
What does G13 signalling lead to?
activates RhoA which activates the actin/myosin interaction
What is ADP released from/
Platelet dense granules
What 3 receptors does ADP bind to in an autocrine fashion?
2 GPCRs & 1 ion channel
What is the main ADP receptor?
P2Y12 (GPCR coupled to Gi)
What does the activation of P2Y12 lead to?
Inhibits adenylate cyclase -> loss of platelet inhibition -> activates PI3-kinase -> activates platelets
What ADP receptor induces Ca2+ signals?
P2Y1
Which ADP receptor is a Ca2+ channel?
P2X1
What is the secondary platelet activator?
Thromboxane A2
What is the role of RAP1?
Activates intergrin alphaIIb beta 3 that binds fibrinogen & mediates aggregation
What is the role of Rho?
switches that control cell shape through regulation of actin cytoskeleton
What are G-proteins activated by?
GTP
What drug blocks TXA2 synthesis?
Aspirin (inhibits COX-1 pathway)
What drug blocks the P2Y12 receptor?
Clopidogrel (ADP not released)
What drug is an antibody againts intergrin alpha IIIb beta 3?
abciximab