Platelet aggregation in response to many agonists is thought to occur by protein kinase C (PKC)-dependent activation of the fibrinogen receptor, cdIb/:33. The adult TGF/31 knockout mouse on a SCID background, which is free of inflammation, exhibits increased bleeding times. Accordingly, platelets from "I'GFe'eI knockout mice fail to aggregate in vitro following stimulation with a number of physiological agonists, including ADP. Furthermoree platelets frome TGFeI knockout mice are unable to bind fluorescently-conjugated fibrinogen following ADP stimulation. However, these platelets change shape and present surface P-selectin, a marker of granule secretion, in response to ADP indicating early signaling events are occurring. In contrast to ADP, platelets from 'I'GF';eI knockout mice aggregate normally and bind fibrinogen in response to thrombin, an agonist which can activate eIIb//33 in a PKC-independent manuer. Platelets from TGF/31 knockout mice also fail to aggregate in response to phorbol myristate acetate, a potent activator of PKC. ttowever, these platelets have similar levels of PKC as platelets from wild type mice. These results sug gest that circulating platelets from TGFeI knockout mice are defective in the component ofintracellular signaling leading to IIbb3 activation. Most likely, this defect occurs at the level of PKC activation and/or involves downstream transducers of PKC signaling.
|Original language||English (US)|
|State||Published - 1997|
ASJC Scopus subject areas
- Molecular Biology