biostudies-literatureKonopatskaya OBritish Heart FoundationWellcome Trust416-24https://www.ebi.ac.uk/biostudies/studies/S-EPMC4773892biostudies-literatureUnknown118(2)Platelets are highly specialized blood cells critically involved in hemostasis and thrombosis. Members of the protein kinase C (PKC) family have established roles in regulating platelet function and thrombosis, but the molecular mechanisms are not clearly understood. In particular, the conventional PKC isoform, PKCα, is a major regulator of platelet granule secretion, but the molecular pathway from PKCα to secretion is not defined. Protein kinase D (PKD) is a family of 3 kinases activated by PKC, which may represent a step in the PKC signaling pathway to secretion. In the present study, we show that PKD2 is the sole PKD member regulated downstream of PKC in platelets, and that the conventional, but not novel, PKC isoforms provide the upstream signal. Platelets from a gene knock-in mouse inBloodProtein kinase C mediates platelet secretion and thrombus formation through protein kinase D2.PMC4773892065975PG/08/049/25130RG/05/015PG/07/118/24152RG/10/006/28299Konopatskaya OGilio KWilliams CMPoole AWNavarro MNCarter DAMatthews SAHarper MTCosemans JMHeemskerk JWLeitges MCantrell DfalseProtein kinase C mediates platelet secretion and thrombus formation through protein kinase D2.Platelets are highly specialized blood cells critically involved in hemostasis and thrombosis. Members of the protein kinase C (PKC) family have established roles in regulating platelet function and thrombosis, but the molecular mechanisms are not clearly understood. In particular, the conventional PKC isoform, PKCα, is a major regulator of platelet granule secretion, but the molecular pathway from PKCα to secretion is not defined. Protein kinase D (PKD) is a family of 3 kinases activated by PKC, which may represent a step in the PKC signaling pathway to secretion. In the present study, we show that PKD2 is the sole PKD member regulated downstream of PKC in platelets, and that the conventional, but not novel, PKC isoforms provide the upstream signal. Platelets from a gene knock-in mouse in2011-01-01T00:00:00Z2011 Jul2025-04-18T22:04:27.884Z2019-03-27T02:10:18ZS-EPMC47738922152752110.1182/blood-2010-10-312199