A tail of two ITAMs: GPVI/FcRγ and FcγRIIa's role in platelet activation and thrombus stability

摘要

Platelets are the ultimate cellular shapeshifters; they are hole pluggers, soldiers against invaders, wound healers, and cargo transporters. One of their more interesting tricks is that they have adapted immune-type receptors to service their role in hemostasis and vascular integrity. Receptors with an immunoreceptor tyrosine-based activation motif (ITAM) that contain two YxxL/I sequences on their cytoplasmic tail are important in supporting the signaling and activation of the integrins that are essential to platelet function. ITAMs and integrins both signal through Src family kinases, with subsequent activation of spleen tyrosine kinase and phospholipase Cγ2, leading to increased cytosolic calcium (Figure 1).1,2 This shared signal transduction pathway allows ITAMs to enhance integrin outside-in signaling and sustain integrin activation.