PROTEIN-KINASE-C REGULATES THE STIMULATED ACCUMULATION OF 3-PHOSPHORYLATED PHOSPHOINOSITIDES IN PLATELETS
PROTEIN-KINASE-C REGULATES THE STIMULATED ACCUMULATION OF 3-PHOSPHORYLATED PHOSPHOINOSITIDES IN PLATELETS
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DOI：
10.1042/bj2780475
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发表时间：
1991-09-01
影响因子：
4.1
通讯作者：
RITTENHOUSE, SE
中科院分区：
文献类型：
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作者：
KING, WG;KUCERA, GL;RITTENHOUSE, SE
我们已经证明，凝血酶或鸟苷5'-[γ -硫]三磷酸（GTP[S]）刺激血小板，两者都能激活磷脂酶C和蛋白激酶C (PKC)，显示出3-磷酸化磷酸肌肽积累（3-PPI）的增强。我们现在报告如下。(1)在渗透化的血小板中加入伪底物肽（RFARK）抑制凝血酶或GTP[S]刺激的PKC可显著抑制3-PPI，而丝氨酸/苏氨酸磷酸酶抑制剂冈田酸可促进3-PPI。PKC活性本身不足以完全激活3-PPI，但对于3-PPI的受体和受体后刺激似乎至关重要，即使酪氨酸磷酸化未受损。(2) adp核糖基化对G(i)的改变仅轻微影响凝血酶对3-PPI的刺激，肾上腺素对G蛋白G(i)的激活对3-PPI没有影响。(3)抑制PKC可阻断活化的血小板衍生生长因子（PDGF）分泌。但PDGF不能促进血小板3-PPI，因此不能解释RFARK对3-PPI的抑制作用。
We have shown that platelets stimulated with thrombin or guanosine 5'-[gamma-thio]triphosphate (GTP[S]), both of which activate phospholipase C and protein kinase C (PKC), show enhancement of 3-phosphorylated phosphoinositide accumulation (3-PPI). We now report the following. (1) Inhibition of thrombin- or GTP[S]-stimulated PKC by pseudosubstrate peptide (RFARK) added to permeabilized platelets markedly inhibits 3-PPI, whereas the serine/threonine phosphatase inhibitor, okadaic acid, promotes 3-PPI. PKC activity, insufficient in itself for fully activating 3-PPI, appears crucial to receptor and post-receptor stimulation of 3-PPI, even when tyrosine phosphorylation is unimpaired. (2) Alteration of G(i) by ADP-ribosylation only slightly affects the stimulation of 3-PPI by thrombin, and activation of the G-protein G(i) by adrenaline has no effect on 3-PPI. (3) Inhibition of PKC blocks activated secretion of platelet-derived growth factor (PDGF). However, PDGF cannot promote platelet 3-PPI, and thus cannot account for the inhibitory effects of RFARK on 3-PPI.