Role of the adapter protein SLP-76 in GPVI-dependent platelet procoagulant responses to collagen

Lorie Leo, Jorge Di Paola, Barbi A. Judd, Gary A. Koretzky, Steven R. Lentz

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


The adapter protein SLP-76 is a critical mediator of signal transduction via the platelet collagen receptor glycoprotein VI (GPVI) and its coreceptor FcRγ. We tested the hypothesis that SLP-76 is required for collagen-induced procoagulant responses in murine platelets. Platelets from SLP-76 null (SLP-76-/-) or heterozygous (SLP-76+/-) mice were activated with the GPVI agonist convulxin, and surface expression of P-selectin (a marker of granule release) and annexin V binding (a marker of procoagulant phospholipid) were determined by flow cytometry. Convulxin induced surface expression of P-selectin in SLP-76+/- platelets, but not SLP-76-/- platelets (P < .01), and failed to stimulate annexin V binding to either SLP-76+/- or SLP-76-/- platelets. Platelet procoagulant activity was measured in a prothrombinase assay. Convulxin did not stimulate procoagulant activity in either SLP-76+/- or SLP-76-/- platelets, but fibrillar collagen produced a 1.9-fold increase in procoagulant activity in both SLP-76+/- and SLP-76-/- platelets (P < .001 versus unstimulated platelets). Similar results were obtained with platelets from FcRγ null mice, for which collagen, but not convulxin, induced procoagulant activity (P < .01). Costimulation with thrombin and collagen produced a further (2.3-fold) increase in procoagulant activity in SLP-76+/- platelets (P < .05), but not in SLP- 76-/- platelets. SLP-76-/- platelets also exhibited less annexin V binding than SLP-76+/- platelets after costimulation with thrombin and convulxln (P < .05). These findings demonstrate that an intact GPVI/FcRγ/SLP-76 signal transduction pathway is not essential for platelet procoagulant activity induced by collagen but is necessary for maximal procoagulant response to costimulation with thrombin plus collagen. Thus, both GPVI-dependent and GPVI-independent pathways contribute to collagen-induced platelet procoagulant activity.

Original languageEnglish
Pages (from-to)2839-2844
Number of pages6
Issue number8
StatePublished - Oct 15 2002


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