ASK1 is a critical MAP3K in platelet activation. Physiological agonists acting through either G-protein-coupled receptors (GPCRs) or glycoprotein VI (GPVI) stimulate secondary messengers and proximal signaling events that activate MAP3Ks, such as ASK1. ASK1 activates MAP2Ks, including MKKs 3, 4, and 6, leading to the stimulation of p38.¹⁰ p38 both phosphorylates cytoplasmic phospholipase A₂ (cPLA₂), stimulating TxA₂ generation, and facilitates integrin activation and granule secretion. JNK, ERK1/2, and ERK5 are controlled by alternative upstream activation mechanisms. Professional illustration by Somersault18:24.