Human Disabled-2 regulates thromboxane A₂ signaling for efficient hemostasis in thrombocytopenia.

ABSTRACT: Understanding platelet protein functions facilitates better assessment of platelet disorders. Megakaryocyte lineage-restricted human Disabled-2 knock-in (hDAB2-KI) mice are generated to delineate the functions of hDab2, a regulator of platelet function, in the control of bleeding associated with thrombocytopenia. Here we show that hDab2-KI mice with thrombocytopenia display decreased bleeding time when compared to the control mice. hDab2 augments thromboxane A₂ (TxA₂) mimetic U46619- but not other agonists-stimulated granule secretion, integrin activation, and aggregation at a lower platelet concentration in vitro. Binding of hDab2 to phosphatidic acid (PA) facilitates formation of the PA-hDab2-AKT complex leading to an increase in U46619-stimulated AKT-Ser473 phospho

SUBMITTER: Tsai HJ 

PROVIDER: S-EPMC11561248 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature