Aggregation-dependent, integrin-mediated increases in cytoskeletally associated PtdInsP2 (4,5) levels in human platelets are controlled by translocation of PtdIns 4-P 5-kinase C to the cytoskeleton.
Thrombin-stimulated aggregation of human platelets promotes an increase in the phosphatidylinositol 4-phosphate (PtdIns 4-P) 5-kinase (PIPkin) activity in the cytoskeleton. This phenomenon is associated with translocation of PIPkin isoform C to the cytoskeleton and with an increase in the amount of phosphatidylinositol bisphosphate (PtdInsP2) bound to the cytoskeletal pellet. All three of these effects are prevented if the platelets are not stirred or if RGD-containing peptides are present, demonstrating that they require integrin activation. All three are also abolished by pretreatment with okadaic acid, which also prevents the aggregation-dependent translocation of pp60(c-src) to the cytoskeleton. The results point to the existence of a cytoskeletally associated PtdInsP2 pool under the control of integrin-mediated signals that act via PIPkin C and suggest that a common, okadaic acid-sensitive mechanism may underlie the aggregation-dependent translocation of certain signalling molecules to the platelet cytoskeleton.
Hinchliffe
K A
KA
The Babraham Institute, Cambridge, UK.
Irvine
R F
RF
Divecha
N
N
D001792:Blood Platelets / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000502:physiology*; D007700:Kinetics; D009842:Oligopeptides / Q000494:pharmacology; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000097:blood*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000097:blood*; D010974:Platelet Aggregation / Q000187:drug effects; D013917:Thrombin / Q000494:pharmacology
D016023:Integrins; D009842:Oligopeptides; D019269:Phosphatidylinositol 4,5-Diphosphate; C047981:arginyl-glycyl-aspartic acid; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase; D013917:Thrombin