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Platelet Activation Inhibitory Signaling

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Integrin alpha 2b beta 3
GPVI
CLEC-2

Src

Csk

Lyn

Fyn

SHIP

CD31/
PECAM-1

G6b

Shp1,2

PI 3-Kinase

PLC-gamma

alpha-2 Adrenergic R
P2Y12
PTGER3

G alpha i

PTGER2,4
PTGIR
Adenosine A2a,A2b R
VIP R1/VPAC1

G alpha s

PTGER3

G alpha z

Adenylyl Cyclase

cAMP

AMP

PKA

Phosphodiesterase 2,3

Caldesmon

Filamin A

G alpha 13

GPIb

HSP27

IP3 Receptor

LASP

MAPK

Phosphodiesterase 3A

Rap1

Rap1GAP2

TRPC6

VASP

Nitric Oxide

L-Arginine

eNOS

Citrulline

Nitric Oxide

Soluble
Guanylyl
Cyclase

cGMP

GMP

Phosphodiesterase 5A

PKG

HSP27

IP3 Receptor

LASP

Myosin Light
Chain Kinase

MAPK

PI 3-Kinase

Phosphodiesterase 5A

Rap1

Rap1GAP2

Thromboxane A2 R

TRPC6

VASP

Inhibition of

Granule Release

Calcium Release

Integrin Activation

Platelet Activation Inhibitory Signaling

Overview of Inhibitory Signaling in Platelets

Unrestricted platelet activation can lead to life threatening thrombosis. In order to maintain control of this process, multiple steps in the platelet activation are regulated by cell surface receptors that block activation signals and by receptors that induce both activating and inhibitory signaling. Healthy vascular endothelial cells release nitric oxide and prostaglandin I2 (prostacyclin) into the blood where they maintain platelet quiescence by blocking granule release and integrin activation.

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