Platelet activation protein kinase

PDGF platelet-derived growth factor RACR receptors for activated protein kinase C... 

Platelet activation occurs in large part via G protein-coupled agonist receptors and intracellular signaling events that involve activation of phospholipase C (PLC). PLC catalyzes the breakdown of plasma membrane inositol phospholipids, resulting in generation of 1,2-diacylglycerol (DAG) and 1,4,5-inositol triphosphate (IP3). DAG activates protein kinase C, and IP3 induces mobilization of calcium from intracellular stores (10). 

DeCoster M. A., Mukheijee R K., Davis R. J., and Bazan N. G. (1998). Platelet-activating factor is a downstream messenger of kainate-induced activation of mitogen-activated protein kinases in primary hippocampal neurons. J. Neurosci. Res. 53 297-303. 

Graves LM, Bomfeldt KE, Raines EW, Potts BC, Macdonald SG, Ross R, Krebs EG. 1993. Protein kinase A antagonizes platelet-derived growth factor-induced signaling by mitogen activated protein kinase in human arterial smooth muscle cells. Proc Natl Acad Sci USA 90 10300-10304. 

Bsbinska A, Ehrlich YH, Komecki E. Activation of human platelets by protein kinase C antibody rede for surface phosphorylation in homeostasis AmJPhysiol 1996 271 H2134-44... 

PAF activates mitogen activated protein kinase (MAP Kinase) in platelets. PAF stimulated P42 MAP Kinase lAPK) in sheep platelets and to a lesser extent P44 MAPK. S6 kinases were also stimulated by PAF (Sa ei et. al., 1993). It is likely that PKC is involved in fiiis process. However, any precise role for platelet MAPK in PAF responses awaits future investigation. 

Borsch-Haubold AG, Kramer RM, Watson SP. Cytosolic phospholipase Aj is phosphorylated in collagen- and thrombin-stimulated human platelets independent of protein kinase C and mitogen-activated protein kinase. JBiol Chem 270 25885-25892,1995. 

PAPKOFF J, Chen R-H, BLENIS J, FORSMAN J. p42 mitogen-activated protein kinase and p90 ribosomal S6 kinase are sriecdvely phosphorylated and activated during thrombin-induced platelet activation and aggregation. Mol Cdl Biol 14 463-472,1994. 

Nakashima S, Chatani Y, Nakamura M, Miyo N, K(dmo M, and Nozawa Y. (1994). Tyrosine phos diotylation and activation of mitogen-activated protein kinases by thrombin in human platelets possible involvement in late aracdiidonic acid release. Biochem. Biophys. Res. Commun. 198, 497-303. 

Kramer RM, Roberts EF,Hyslop PA UtterbackBG,HuiKY, and Jakubowski JA (1995). Differendal activation of cytosolic diospholipase A2 (cPLA2) by thrombin and thrombin receptor agonist peptide in human platelets. Evidence for activation of cPLA2 indepoident of the mitOgen-activated protein kinases ERKl/2. J. Biol. Chem. 270,14816-4823. 

Kramer RM, Roberts EF, Um SL, Borsch-Haubold AO, Watson SP, Fisher MJ, and Jakubowski JA (1996). p38 mitogen-activated protein kinase jdiosphorylates cytosolic phospholipase A2 (cPLA2) in thrombin-stimulated platelets. Evidence that proline-directed phosph lation is not required ftn-mobilization of arachidonic acid by cPLA2. J. Biol. Chem. 271,27723-27729. 

Borsch-Haubold AG, Kramer RM, and Watson SP. (1997). Pho orylation and activation of cytosolic phospholipase A2 by 38-kDa mitogen-activated protein kinase in collagen-stimulated human platelets. Eur. J. Biochem. 245,751-759. 

Lipoxygenase metabolites of arachidonic acid such as 12-hydroxyeicosa-tetraenoic acid (12-HETE) have been shown to be involved in the release of neurotiansmitters and other cellular functions (92-94). Basal generation of 12-HETE has been reported to be about 3.7-fold greater in SHR than in WKY platelets (95,96). Arachidonic acid has been shown to stimulate platelets by activating protein kinase C, by a prostaglandin-independent mechanism (97). It is possible that the lipoxygenase metabolites of arachidonic acid may also be involved in altered reactivity in hypertension. 

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