Critical redundant functions of the adapters Grb2 and Gads in platelet (hem)ITAM signaling in mice.

Critical redundant functions of the adapters Grb2 and Gads in platelet (hem)ITAM signaling in mice. Platelets. 2020 Jan 16;:1-11 Authors: Vögtle T, Baig AA, Volz J, Duchow TB, Pleines I, Dütting S, Nitschke L, Watson SP, Nieswandt B Abstract Platelets are essential for normal hemostasis; however, pathological conditions can also trigger unwanted platelet activation precipitating thrombosis and ischemic damage of vital organs such as the heart or brain. Glycoprotein (GP)VI- and C-type lectin-like receptor 2 (CLEC-2)-mediated (hem)immunoreceptor tyrosine-based activation motif (ITAM) signaling represents a major pathway for platelet activation. The two members of the Growth-factor receptor-bound protein 2 (Grb2) family of adapter proteins expressed in platelets - Grb2 and Grb2-related adapter protein downstream of Shc (Gads) - are part of the hem(ITAM) signaling cascade by forming an adapter protein complex with linker for activation of T cells (LAT). To date, a possible functional redundancy between these two adapters in platelet activation has not been investigated. We here generated megakaryocyte- and platelet-specific Grb2/Gads double knockout (DKO) mice and analyzed their platelet function in vitro and in vivo. The DKO platelets exhibited virtually abolished (hem)ITAM signaling whereas only partial defects were seen in Grb2 or Gads single-deficient platelets. This was based on impaired phosphorylation of key molecules in the (he...
Source: Platelets - Category: Hematology Tags: Platelets Source Type: research