FIGURE 7.

Schematic illustration of proposed role of PI3K and AKT signaling pathway in procoagulant platelets in severe COVID‐19. Proposed mechanism presenting the role of PI3K and AKT signaling pathways in platelet function via stimulation of FcγRIIA‐receptor in severe COVID‐19 patients. After stimulation by SARS‐CoV‐2 infection, FcγRIIA interacts with immunoreceptor tyrosine‐based activation motif (ITAM), upon which phosphatidylinositol 3‐kinase (PI3K) is activated and subsequently induces downstream signal pathways, activating the serine/threonine protein kinase B (PKB/AKT) on Ser473. This leads to serine and/or threonine phosphorylation of a range of downstream substrates which often themselves are kinase/phosphatases and signaling molecules which mediate the main platelet activation responses by α‐granules externalization and PS exposure, which leads to monocytes adhesion and endothelia dysfunction. AKT, AKT8 virus oncogene cellular homolog, kinase; FC, flow cytometry; mAb, mouse antibody; PI3K, phosphoinositide‐3‐kinase; PS, phosphatidylserine; RT, room temperature