Figure 2.

Schematic overview of inside-out signalling in platelets. Agonist activation of G protein-coupled receptor triggers signalling pathways with key signalling proteins like phospholipase C (PLC), protein kinase C (PKC) and phosphatidylinositide-3-kinase (PI3K). Increased Ca²⁺ will lead to activation of CalDAG-GEFI that will activate Ras-related protein 1 (RAP1). RASA3 acts as a negative regulator of RAP1 activation, and RASA3 activity is restricted by PI3K activation. Through the separation of the talin head and tail domain, the talin head domain associates with the cytoplasmic tail of the β3 subunit, converting the integrin αIIbβ₃ from the inactive to the active form.