scholarly journals Role of a JAK3-dependent Biochemical Signaling Pathway in Platelet Activation and Aggregation

2001 ◽  
Vol 276 (21) ◽  
pp. 17815-17822 ◽  
Author(s):  
Heather E. Tibbles ◽  
Alexei Vassilev ◽  
Heather Wendorf ◽  
Dawn Schonhoff ◽  
Dan Zhu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Platelet Activation

Abstract 598: A Platelet Glycoprotein Ib-IX-specific 14-3-3/Rac1/LIMK1 Signaling Pathway Promotes Thrombin-Induced Platelet Activation

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Brian Estevez ◽  
Keegan Delaney ◽  
Aleksandra Stojanovic-Terpo ◽  
Xiaoping Du
Keyword(s):  
Binding Site ◽  
Signaling Pathway ◽  
Platelet Activation ◽  
Intracellular Signaling ◽  
Low Dose ◽  
Cell Model ◽  
Chinese Hamster ◽  
Platelet Glycoprotein ◽  
Protease Activated Receptors

Rationale: Thrombin-induced platelet activation requires protease-activated receptors. However, the platelet glycoprotein (GP) Ib-IX complex (GPIb-IX) binds to thrombin and is important for low dose thrombin-induced platelet activation. It is unclear how GPIb-IX promotes thrombin-induced platelet activation. Objective: To clearly elucidate the mechanism by which GPIb-IX promotes thrombin-induced platelet activation. Methods and Results: We reconstituted GPIb-IX (GPIb) /Protease-activated receptors (PARs) cooperativity in response to thrombin in Chinese Hamster Ovary (CHO) cells expressing PAR1. Thrombin-induced PAR1-dependent calcium signaling was significantly enhanced by GPIb expression. This effect of GPIb appears to require GPIb signaling, as mutation of a cytoplasmic binding site for an intracellular signaling molecule, 14-3-3, in GPIbα abolished the stimulatory effect of GPIb. The importance of GPIb-IX-14-3-3 interaction in promoting thrombin-induced platelet activation was also shown by pretreating human platelets with MPαC, an inhibitory peptide based on a critical 14-3-3 binding site in the C-terminus of GPIbα, which inhibited thrombin-induced platelet activation, but did not affect thrombin binding to platelets. Furthermore, 14-3-3 binding site deletion in GPIbα or MPαC-pretreatment inhibited thrombin-induced activation of Rac1 and phosphorylation of LIMK1. To determine the role of the Rac1/LIMK1 signaling pathway in mediating thrombin-induced GPIb signaling and platelet activation, we examined the effects of Rac1 knockout, LIMK1 knockout and Rac1-inhibitor on low dose thrombin-induced calcium response and platelet activation. Rac1 inhibitor, NSC23766, abolished the GPIb-dependent cell response in a reconstituted CHO cell model. Rac1 knockout platelets showed diminished platelet response to thrombin and were not different from wild type platelets in the presence of MPαC. Importantly, LIMK1-/- platelets display defective thrombin-induced platelet activation but enhanced PAR4-activating peptide induced platelet activation. Conclusions: The stimulatory role of GPIb in thrombin-induced platelet activation requires a thrombin-induced GPIb-specific 14-3-3/Rac1/LIMK1 signaling pathway.

Role of a Janus kinase 2-dependent signaling pathway in platelet activation

2014 ◽  
Vol 133 (6) ◽  
pp. 1088-1096 ◽  
Author(s):  
Wan-Jung Lu ◽  
Kao-Chang Lin ◽  
Shih-Yi Huang ◽  
Philip Aloysius Thomas ◽  
Yu-Hua Wu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Platelet Activation ◽  
Janus Kinase ◽  
Janus Kinase 2 ◽  
Dependent Signaling Pathway

scholarly journals The role of PI3K/Akt signaling pathway in non‐physiological shear stress‐induced platelet activation

2019 ◽  
Vol 43 (9) ◽  
pp. 897-908 ◽  
Author(s):  
Zengsheng Chen ◽  
Tieluo Li ◽  
Kafayat Kareem ◽  
Douglas Tran ◽  
Bartley P. Griffith ◽  
...  
Keyword(s):  
Shear Stress ◽  
Signaling Pathway ◽  
Platelet Activation ◽  
Akt Signaling ◽  
Akt Signaling Pathway

285: The Role of the NF-κB Signaling Pathway in the Pathogenesis of Interstitial Cystitis

2006 ◽  
Vol 175 (4S) ◽  
pp. 95-95
Author(s):  
Raymond R. Rackley ◽  
Mei Kuang ◽  
Ashwin A. Vaze ◽  
Joseph Abdelmalak ◽  
Sandip P. Vasavada ◽  
...  
Keyword(s):  
Interstitial Cystitis ◽  
Signaling Pathway

On The Mechanism Of Heparin-Induced Potentiation Of Platelet Aggregation

1981 ◽  
Author(s):  
M Yamamoto ◽  
K Watanabe ◽  
Y Ando ◽  
H Iri ◽  
N Fujiyama ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Coagulation Factors ◽  
Marked Enhancement ◽  
Matrix Bound ◽  
Induced Aggregation ◽  
Aggregation Of Platelets ◽  
Plasma Heparin

It has been suggested that heparin caused potentiation of aggregation induced by ADP or epinephrine. The exact mechanism of heparin-induced platelet activation, however, remained unknown. In this paper, we have investigated the role of anti-thrombin III ( AT ) in heparin-induced platelet activation using purified AT and AT depleted plasma. When ADP or epinephrine was added to citrated PRP one minute after addition of heparin ( 1 u/ml, porcine intestinal mucosal heparin, Sigma Co. USA ), marked enhancement of platelet aggregation was observed, compared with the degree of aggregation in the absence of heparin. However, in platelet suspensions prepared in modified Tyrode’s solution, heparin exhibited no potentiating effect on platelet aggregation induced by epinephrine or ADP. Potentiation of epinephrine- or ADP-induced platelet aggregation by heparin was demonstrated when purified AT was added to platelet suspensions at a concentration of 20 μg/ml. AT depleted plasma, which was prepared by immunosorption using matrix-bound antibodies to AT, retained no AT, while determination of α1-antitrypsinα2- macroglobulin and fibrinogen in AT depleted plasma produced values which corresponded to those of the original plasma when dilution factor was taken into account. The activities of coagulation factors were also comparable to those of the original plasma. Heparin exhibited potentiating effect on ADP- or epinephrine-induced aggregation of platelets in original plasma, but no effect in AT depleted plasma. When purified AT was added back to AT depleted plasma at a concentration of 20 μg/ml, potentiation of platelet aggregation by heparin was clearly demonstrated.Our results suggest that effect of heparin on platelet aggregation is also mediated by anti-thrombin III.

Biological role of AKT, and regulation of AKT signaling pathway by thymoquinone: perspectives in cancer therapeutics

2020 ◽  
Vol 20 ◽  
Author(s):  
Md. Junaid ◽  
Yeasmin Akter ◽  
Syeda Samira Afrose ◽  
Mousumi Tania ◽  
Md. Asaduzzaman Khan
Keyword(s):  
Clinical Trials ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Inhibitory Effect ◽  
Akt Signaling ◽  
Review Article ◽  
Therapeutic Drug ◽  
Akt Signaling Pathway ◽  
Anti Cancer

Background: AKT/PKB is an important enzyme with numerous biological functions, and its overexpression is related to the carcinogenesis. AKT stimulates different signaling pathways that are downstream of activated tyrosine kinases and phosphatidylinositol 3-kinase, hence functions as an important target for anti-cancer drugs. Objective: In this review article, we have interpreted the role of AKT signaling pathways in cancer and natural inhibitory effect of Thymoquinone (TQ) in AKT and its possible mechanism. Method: We have collected the updated information and data on AKT, their role in cancer and inhibitory effect of TQ in AKT signaling pathway from google scholar, PubMed, Web of Science, Elsevier, Scopus and many more. Results: There are many drugs already developed, which can target AKT, but very few among them have passed clinical trials. TQ is a natural compound, mainly found in black cumin, which has been found to have potential anti-cancer activities. TQ targets numerous signaling pathways, including AKT, in different cancers. In fact, many studies revealed that AKT is one of the major targets of TQ. The preclinical success of TQ suggests its clinical studies on cancer. Conclusion: This review article summarizes the role of AKT in carcinogenesis, its potent inhibitors in clinical trials, and how TQ acts as an inhibitor of AKT and TQ’s future as a cancer therapeutic drug.

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