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Comment
. 2018 Sep;16(9):1901-1904.
doi: 10.1111/jth.14232. Epub 2018 Aug 16.

PDK1 governs thromboxane generation and thrombosis in platelets by regulating activation of Raf1 in the MAPK pathway: comment

P Patel  1 , K Golla  1 , U P Naik  1
Affiliations
Free PMC article
Comment

PDK1 governs thromboxane generation and thrombosis in platelets by regulating activation of Raf1 in the MAPK pathway: comment

P Patel et al. J Thromb Haemost. 2018 Sep.
Free PMC article
No abstract available

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Conflict of interest statement

Disclosure of Conflicts of Interest

The authors state that they have no conflict of interest.

Figures

Figure 1
Figure 1. PDK1 and ASK1 regulate ADP-induced cPLA2 phosphorylation and TxA2 generation through two distinct mechanisms
(A) Western blot of lysates of washed murine platelets (2×108 platelets/mL) isolated from WT or Ask1−/− mice and stimulated with 2MeSADP (2.5 or 50nM). Blots were probed with phospho-specific antibodies against cPla2-Ser505, Erk1/2, and p38 as indicated. Blots were reprobed with anti-Hsc70, anti-p38, and anti-Erk1/2 to ensure equal loading. (B) Quantitation of optical density of bands from A for cPla2-Ser505 (Bi–ii), Erk1/2 (Biii–iv), and p38 (Bv–vi) when stimulated with either 2.5nM (Bi, iii, v) or 50nM (Bii, iv, vi) 2MeSADP. (C) Western blot of lysates of washed human platelets (4×108 platelets/mL) pretreated with GS-4997 for 20 minutes and stimulated with 2MeSADP (100nM) for 1, 3, and 5 minutes. Blots were processed as in A. (D) Quantitation of optical density of bands from C for ASK1-Thr845 (Di), cPLA2-Ser505 (Dii), ERK1/2 (Diii), and p38 (Div). (E) Western blot of human platelet lysate (4×108 platelets/mL) pretreated with GS-4997 and stimulated with convulxin (50ng/mL) for 3 minutes. (F) Quantitation of band intensity was expressed as percent inhibition from E. (G) Schematic representation of the signaling mechanism (based on our observations and those of Manne et al.,) describing the relationship between ASK1/p38 and PDK1/ERK1/2 as it relates to cPLA2-Ser505 phosphorylation. Two-way ANOVA (B & D) and liner regression analysis (F) were performed using Graphpad Prism Software. Representative blots are shown in panel (A, C, and E). Results are from 3 independent experiments.
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