Calpain regulation of integrin alpha IIb beta 3 signaling in human platelets.
Efficient platelet adhesion and aggregation at sites of vascular injury requires the synergistic contribution of multiple adhesion receptors. The initial adhesion of platelets to subendothelial matrix proteins involves GPIb/V/IX and one or more platelet integrins, including integrin alpha IIb beta 3, alpha 2 beta 1, alpha 5 beta 1 and possibly alpha 6 beta 1. In contrast, platelet-platelet adhesion (platelet cohesion or aggregation) is mediated exclusively by GPIb/V/IX and integrin alpha IIb beta 3. Integrin alpha IIb beta 3 is a remarkable receptor that not only stabilizes platelet-vessel wall and platelet-platelet adhesion contacts, but also transduces signals necessary for a range of other functional responses. These signals are linked to cytoskeletal reorganization and platelet spreading, membrane vesiculation and fibrin clot formation, and tension development on a fibrin clot leading to clot retraction. This diverse functional role of integrin alpha IIb beta 3 is reflected by its ability to induce the activation of a broad range of signaling enzymes that are involved in membrane phospholipid metabolism, protein phosphorylation, calcium mobilization and activation of small GTPases. An important calcium-dependent signaling enzyme involved in integrin alpha IIb beta 3 outside-in signaling is the thiol protease, calpain. This enzyme proteolyses a number of key structural and signaling proteins involved in cytoskeletal remodeling and platelet activation. These proteolytic events appear to play a potentially important role in modulating the adhesive and signaling function of integrin alpha IIb beta 3.
Australian Centre for Blood Diseases, Department of Medicine, Monash Medical School, Box Hill Hospital, Victoria, Australia.
S M
SM
Schoenwaelder
Y
Y
Yuan
S P
SP
Jackson
D001792:Blood Platelets / Q000737:chemistry / Q000201:enzymology / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D010973:Platelet Adhesiveness / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects
D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D002154:Calpain; D002118:Calcium