The roles of LAT in platelet signaling induced by collagen, TxA2, or ADP.
The work presented here demonstrates that platelets from mice lacking LAT (linker for the activation of T cells) show reversible aggregation in response to concentrations of collagen that cause TxA2/ADP-dependent irreversible aggregation of control platelets. The aggregation defect of the LAT-deficient platelets was shown to be the result of almost no TxA2 production and significantly diminished ADP secretion. In contrast, the LAT deficiency does not affect aggregation induced by high concentrations of collagen because that aggregation is not dependent on TxA2 and/or ADP. Even though ADP and TxA2 provide amplification signals for platelet activation in response to low concentrations of collagen, LAT-deficient platelets hyperaggregate to low levels of U46619, a TxA2 analog, or ADP. Though the mechanism(s) of costimulatory signals by collagen, ADP, and TxA2 remains unidentified, it is clear that LAT plays a positive role in collagen-induced, TxA2/ADP-dependent aggregation, and a negative role in TxA2 or ADP-induced platelet aggregation.
Cho
Moon J
MJ
Department of Microbiology and Molecular Cell Sciences, University of Memphis, Memphis, Tennessee 38152, USA.
Pestina
Tamara I
TI
Steward
Shirley A
SA
Jackson
Carl W
CW
Kent Gartner
T
T
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D048868:Adaptor Proteins, Signal Transducing; D000244:Adenosine Diphosphate / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003094:Collagen / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010974:Platelet Aggregation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013928:Thromboxane A2 / Q000096:biosynthesis / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D048868:Adaptor Proteins, Signal Transducing; D000906:Antibodies; D002352:Carrier Proteins; C491734:Lat protein, mouse; D008565:Membrane Proteins; D010750:Phosphoproteins; D014662:Vasoconstrictor Agents; D016718:Arachidonic Acid; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D003094:Collagen