scholarly journals Role of type 1 and type 2A phosphatases in signal transduction of platelet-activating-factor-stimulated rabbit platelets

1994 ◽  
Vol 301 (2) ◽  
pp. 531-537 ◽  
Author(s):  
C T Murphy ◽  
J Westwick
Keyword(s):  
Signal Transduction ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Platelet Activating Factor ◽  
Signal Transduction Pathway ◽  
Calyculin A ◽  
Signal Molecule ◽  
Kinase C

Calyculin A, the potent inhibitor of type 1 (PP1) and type 2A (PP2A) phosphatases, has been employed in order to investigate the role of endogenously activated PP1/PP2A in the signal-transduction pathway of platelet-activating-factor (PAF)-stimulated platelets. Calyculin A alone caused an increase in protein phosphorylation in unstimulated platelets, with the detection of a number of newly phosphorylated proteins, whereas in PAF-stimulated platelets phosphorylation of the major substrates of protein kinase C and myosin light-chain kinase were no longer transient, but phosphorylation was sustained. PP1/PP2A appear to play a role in Ca2+ homoeostasis, as inhibition of PP1/PP2A caused an inhibition of Ca2+ mobilization and Ca2+ influx through the plasma membrane in PAF-stimulated platelets. The effect of calyculin A on Ca2+ mobilization correlated with the observed inhibition of the production of the signal molecule Ins(1,4,5)P3. The release reaction (which is a Ca(2+)-dependent event) was also inhibited by calyculin A. The results are discussed in relation to the possible role of protein kinase C in mediating the events leading to the effects observed with calyculin A.

scholarly journals Direct evidence for a key role of protein kinase C in the development of vasospasm after subarachnoid hemorrhage

1992 ◽  
Vol 76 (4) ◽  
pp. 635-639 ◽  
Author(s):  
Shigeru Nishizawa ◽  
Nobukazu Nezu ◽  
Kenichi Uemura
Keyword(s):  
Signal Transduction ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Direct Evidence ◽  
Control Group ◽  
Content Type ◽  
Kinase C ◽  
Protein Kinase C Activity ◽  
Fine Print

✓ Vascular contraction is induced by the activation of intracellular contractile proteins mediated through signal transduction from the outside to the inside of cells. Protein kinase C plays a crucial role in this signal transduction. It is hypothesized that protein kinase C plays a causative part in the development of vasospasm after subarachnoid hemorrhage (SAH). To verify this directly, the authors measured protein kinase C activity in canine basilar arteries in an SAH model with (γ-32P)adenosine triphosphate and the data were compared to those in a control group. Protein kinase C is translocated to the membrane from the cytosol when it is activated, and the translocation is an index of the activation; thus, protein kinase C activity was measured both in the cytosol and in the membrane fractions. Protein kinase C activity in the membrane in the SAH model was remarkably enhanced compared to that in the control group. The percentage of membrane activity to the total was also significantly greater in the SAH vessels than in the control group, and the percentage of cytosol activity in the SAH group was decreased compared to that in the control arteries. The results indicate that protein kinase C in the vascular smooth muscle was translocated to the membrane from the cytosol and was activated when SAH occurred. It is concluded that this is direct evidence for a key role of protein kinase C in the development of vasospasm.

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