scholarly journals Protein kinase C and P 2 Y 12 take center stage in thrombin‐mediated activation of mammalian target of rapamycin complex 1 in human platelets

2014 ◽  
Vol 12 (5) ◽  
pp. 748-760 ◽  
Author(s):  
S. F. Moore ◽  
R. W. Hunter ◽  
I. Hers
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Mammalian Target Of Rapamycin ◽  
Human Platelets ◽  
Target Of Rapamycin ◽  
Center Stage ◽  
Kinase C

scholarly journals Induction of autophagy by palmitic acid via protein kinase C-mediated signaling pathway independent of mTOR (mammalian target of rapamycin).

2014 ◽  
Vol 289 (14) ◽  
pp. 9501-9501 ◽  
Author(s):  
Shi Hao Tan ◽  
Guanghou Shui ◽  
Jing Zhou ◽  
Jasmine Jia'En Li ◽  
Boon-Huat Bay ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Palmitic Acid ◽  
Signaling Pathway ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Kinase C

scholarly journals Induction of Autophagy by Palmitic Acid via Protein Kinase C-mediated Signaling Pathway Independent of mTOR (Mammalian Target of Rapamycin)

2012 ◽  
Vol 287 (18) ◽  
pp. 14364-14376 ◽  
Author(s):  
Shi Hao Tan ◽  
Guanghou Shui ◽  
Jing Zhou ◽  
Jasmine Jia'En Li ◽  
Boon-Huat Bay ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Palmitic Acid ◽  
Signaling Pathway ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Kinase C

scholarly journals The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C

2008 ◽  
Vol 27 (14) ◽  
pp. 1932-1943 ◽  
Author(s):  
Valeria Facchinetti ◽  
Weiming Ouyang ◽  
Hua Wei ◽  
Nelyn Soto ◽  
Adam Lazorchak ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Kinase C

Comparison of the modes of action of Ca2+ ionophore A23187 and thrombin in protein kinase C activation in human platelets

FEBS Letters ◽  
1985 ◽  
Vol 192 (1) ◽  
pp. 4-8 ◽  
Author(s):  
Kimihiko Sano ◽  
Hajime Nakamura ◽  
Tamotsu Matsuo ◽  
Yasuhiro Kawahara ◽  
Hisashi Fukuzaki ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Human Platelets ◽  
Ionophore A23187 ◽  
Modes Of Action ◽  
Kinase C ◽  
Protein Kinase C Activation

EXOGENOUSLY ADDED DIACYLGLYCEROL (DAG) AND ELEVATED INTRACELLULAR Ca2+ LEVELS CANNOT SUBSTITUTE FOR PROSTAGLANDIN END0PER0XIDES/ THROMBOXANE ki IN MEDIATING WEAK AGONIST-INDUCED PLATELET SECRETION

1987 ◽  
Author(s):  
S Krishnamurthi ◽  
V V Kakkar
Keyword(s):  
Protein Kinase C ◽  
Platelet Aggregation ◽  
Protein Kinase ◽  
Human Platelets ◽  
Similar Degree ◽  
Low Concentration ◽  
Kinase C ◽  
Platelet Secretion

We have compared the abilities of exogenously added U46619, the PG endoperoxide analogue and, sn-l-oleoyl 2-acetylglycerol (OAG) and sn-1,2-dioctanoylglycerol (diCg), the membrane-permeant DAG analogues, at restoring weak agonist-induced secretion in indomethacin (10μM)-treated platelets (I-PL) in the absence of endogenous PG/Tx synthesis. [14C]-5HT secretion from pre-loaded, washed human platelets was correlated with the levels of [Ca2+]i, using platelets loaded with quin 2. Concentrations of OAG (62-125μM) and diCg (15-30μM), which have previously been shown to be fully effective at activating protein kinase C, failed to significantly enhance [14C]-5HT secretion in combination with ADP (10μM), adrenaline (10μM) or PAF (0.2μM) although they potentiated platelet aggregation, when added 10-30 sec after these agonists to I-PL. eg ADP-0%, 30jiM diCg-9.8%, ADP+diCg-11.9%, 5HT release (p>O.05). In contrast, a low concentration of U46619 (0.2μM), that induced no aggregation, [14C]-5HT secretion or rise in [Ca2+]i levels on its own, was able to synergize strongly at potentiating secretion in combination with all three weak agonists examined, as well as in combination with OAG and diCg (U46619-0%, ADP+U46619-20.4%, U46619+30μM diC8-48% 5HT release) . The greater effectiveness of U46619 at potentiating secretion in combination with the weak agonists was not related to different degrees of [Ca2+]i mobilisation, as ADP and PAF-induced rise in [Ca2+]i occurred to a similar degree in the presence of U46619 and diCg. At a higher concentration of U46619 (0.6μM), which was maximally effective at inducing secretion and elevating [Ca2+]i levels on its own, addition of the weak agonists or OAG or diCg, along with U46619, resulted in a further enhancement of secretion which was independent of changes in [Ca2+]i levels. The results demonstrate that U46619 but not OAG or diCg, is able to fully restore weak agonist-induced secretion in indomethacin-treated platelets, suggesting that the actions of endogenously formed PG endoperoxides/TxA2 cannot be substituted by DAG and raised [Ca2+]i levels and, may be mediated via a mechanism additional to that involving these mediators.

Involvement of proline-rich tyrosine kinase 2 in platelet activation: tyrosine phosphorylation mostly dependent on αIIbβ3 integrin and protein kinase C, translocation to the cytoskeleton and association with Shc through Grb2

2000 ◽  
Vol 347 (2) ◽  
pp. 561-569 ◽  
Author(s):  
Tsukasa OHMORI ◽  
Yutaka YATOMI ◽  
Naoki ASAZUMA ◽  
Kaneo SATOH ◽  
Yukio OZAKI
Keyword(s):  
Protein Kinase C ◽  
Platelet Aggregation ◽  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Tyrosine Phosphorylation ◽  
Human Platelets ◽  
Sh2 Domain ◽  
Kinase C ◽  
Tyrosine Kinase 2 ◽  
Αiibβ3 Integrin

Proline-rich tyrosine kinase 2 (Pyk2) (also known as RAFTK, CAKβ or CADTK) has been identified as a member of the focal adhesion kinase (FAK) family of protein-tyrosine kinases and it has been suggested that the mode of Pyk2 activation is distinct from that of FAK. In the present study we investigated the mode of Pyk2 activation in human platelets. When platelets were stimulated with thrombin, Pyk2, as well as FAK, was markedly tyrosine-phosphorylated, in a manner mostly dependent on αIIbβ3 integrin-mediated aggregation. The residual Pyk2 tyrosine phosphorylation observed in the absence of platelet aggregation was completely abolished by pretreatment with BAPTA/AM [bis-(o-aminophenoxy)ethane-N,N,Nʹ,Nʹ-tetra-acetic acid acetoxymethyl ester]. The Pyk2 phosphorylation was inhibited by protein kinase C (PKC) inhibitors at concentrations that inhibited platelet aggregation. In contrast, direct activation of PKC with the active phorbol ester PMA induced the tyrosine phosphorylation of Pyk2 and FAK but only when platelets were fully aggregated with the exogenous addition of fibrinogen (the ligand for αIIbβ3 integrin). Furthermore, PMA-induced Pyk2 (and FAK) tyrosine phosphorylation was also observed when platelets adhered to immobilized fibrinogen. The activation of the von Willebrand factor (vWF)--glycoprotein Ib pathway with botrocetin together with vWF failed to induce Pyk2 (and FAK) tyrosine phosphorylation. Most Pyk2 and FAK was present in the cytosol and membrane skeleton fractions in unstimulated platelets. When platelets were stimulated with thrombin, both Pyk2 and FAK were translocated to the cytoskeleton in an aggregation-dependent manner. In immunoprecipitation studies, Pyk2, as well as FAK, seemed to associate with Shc through Grb2. With the use of glutathione S-transferase fusion proteins containing Shc-SH2, Grb2-SH2, and Grb2 N-terminal and C-terminal SH3 domains, it was implied that the proline-rich region of Pyk2 (and FAK) binds to the N-terminal SH3 domain of Grb2 and that the phosphotyrosine residue of Shc binds to the SH2 domain of Grb2. Although Pyk2 and FAK have been reported to be differentially regulated in many cell types, our results suggest that, in human platelets, the mode of Pyk2 activation is mostly similar to that of FAK, in terms of αIIbβ3 integrin-dependent and PKC-dependent tyrosine phosphorylation. Furthermore, Pyk2, as well as FAK, might have one or more important roles in post-aggregation tyrosine phosphorylation events, in association with the cytoskeleton and through interaction with adapter proteins including Grb2 and Shc.

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