Phospholipase D in platelets and other cells.
Phospholipase D (PLD) hydrolyses phosphatidylcholine to phosphatidic acid (PA) and choline, where PA is considered to be the main effector of PLD's functions in cells. PA can act as a second messenger itself or as a precursor for Diacylglycerols (DAG) and lyso-PA. PA is reported to be involved in protein recruitment in membranes and membrane fusion processes, and PLD is proposed to play a role in signalling, intracellular transport and cytoskeletal rearrangements in cells. Protein kinase C (PKC), small G proteins and phosphatidylinositol-(4,5)-bis-phosphate (PIP(2)) are all central in the regulation of PLD activity; however, PLD has also been shown to be regulated by Ca(2+), protein tyrosine kinases and other kinases. Two isoforms of PLD have been cloned, PLD1 and 2, which are also present in platelets. In vitro PLD1 has a low basal activity and is readily activated by PKC, Adenosine diphosphate(ADP)-ribosylation factor (ARF) and Rho family members, while in contrast PLD2 shows a constitutive high basal activity and is not as easily activated by the factors mentioned above. The two PLD isoforms may have different localization and play different roles in cells. The role and regulation of PLD in platelets are largely unknown. However, PLD in platelets is activated by physiological activators like thrombin and collagen and inhibited by PKA, implying that PLD is involved in established signalling pathways in these cells. Activation by thrombin is stimulated by extracellular Ca(2+) and accompanied by translocation from cytosol to the plasma membrane area. Thrombin-induced PLD activity is dependent of autocrine stimulation. Possible roles for PLD in platelets include lysosomal secretion and actin polymerization. In this review we present the knowledge of PLD from other cells together with findings from platelets and demonstrate that PLD in platelets seems to have much of the same properties as in other cells, which implies that knowledge on PLD from other cells can be used in identifying activation mechanisms and roles in platelets.
Vorland
M
M
Department of Biomedicine, University of Bergen, Bergen, Norway. marta.vorland@biomed.uib.no
Thorsen
V A T
VA
Holmsen
H
H
D001792:Blood Platelets / Q000201:enzymology* / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D010739:Phospholipase D / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction
D011493:Protein Kinase C; D010739:Phospholipase D; D019204:GTP-Binding Proteins