scholarly journals Role of proteolytic activation of protein kinase Cδ in the pathogenesis of prion disease

Prion ◽  
2014 ◽  
Vol 8 (1) ◽  
pp. 143-153 ◽  
Author(s):  
Dilshan S Harischandra ◽  
Naveen Kondru ◽  
Dustin P Martin ◽  
Arthi Kanthasamy ◽  
Huajun Jin ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Prion Disease ◽  
Proteolytic Activation ◽  
Protein Kinase Cδ

Role of Proteolytic Activation of Protein Kinase Cδ in Oxidative Stress-Induced Apoptosis

2003 ◽  
Vol 5 (5) ◽  
pp. 609-620 ◽  
Author(s):  
Anumantha G. Kanthasamy ◽  
Masashi Kitazawa ◽  
Arthi Kanthasamy ◽  
Vellareddy Anantharam
Keyword(s):  
Oxidative Stress ◽  
Protein Kinase ◽  
Proteolytic Activation ◽  
Induced Apoptosis ◽  
Protein Kinase Cδ

scholarly journals The pathophysiologic role of the protein kinase Cδ pathway in the intervertebral discs of rabbits and mice: In vitro, ex vivo, and in vivo studies

2012 ◽  
Vol 64 (6) ◽  
pp. 1950-1959 ◽  
Author(s):  
Michael B. Ellman ◽  
Jae-Sung Kim ◽  
Howard S. An ◽  
Jeffrey S. Kroin ◽  
Xin Li ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Ex Vivo ◽  
Intervertebral Discs ◽  
In Vivo Studies ◽  
Protein Kinase Cδ

scholarly journals Characterization of Integrin αIIbβ3-Mediated Outside-in Signaling by Protein Kinase Cδ in Platelets

2020 ◽  
Vol 21 (18) ◽  
pp. 6563
Author(s):  
Preeti Kumari Chaudhary ◽  
Sanggu Kim ◽  
Youngheun Jee ◽  
Seung-Hun Lee ◽  
Soochong Kim
Keyword(s):  
Protein Kinase ◽  
Kinase Inhibitor ◽  
Wild Type ◽  
Clot Retraction ◽  
Integrin Αiibβ3 ◽  
Tyrosine Kinase 2 ◽  
Platelet Spreading ◽  
Protein Kinase Cδ

Engagement of integrin αIIbβ3 promotes platelet–platelet interaction and stimulates outside-in signaling that amplifies activation. Protein kinase Cδ (PKCδ) is known to play an important role in platelet activation, but its role in outside-in signaling has not been established. In the present study, we determined the role of PKCδ and its signaling pathways in integrin αIIbβ3-mediated outside-in signaling in platelets using PKCδ-deficient platelets. Platelet spreading to immobilized fibrinogen resulted in PKCδ phosphorylation, suggesting that αIIbβ3 activation caused PKCδ activation. αIIbβ3-mediated phosphorylation of Akt was significantly inhibited in PKCδ -/- platelets, indicating a role of PKCδ in outside-in signaling. αIIbβ3-mediated PKCδ phosphorylation was inhibited by proline-rich tyrosine kinase 2 (Pyk2) selective inhibitor, suggesting that Pyk2 contributes to the regulation of PKCδ phosphorylation in outside-in signaling. Additionally, Src-family kinase inhibitor PP2 inhibited integrin-mediated Pyk2 and PKCδ phosphorylation. Lastly, platelet spreading was inhibited in PKCδ -/- platelets compared to the wild-type (WT) platelets, and clot retraction from PKCδ -/- platelets was markedly delayed, indicating that PKCδ is involved in the regulation of αIIbβ3-dependent interactivities with cytoskeleton elements. Together, these results provide evidence that PKCδ plays an important role in outside-in signaling, which is regulated by Pyk2 in platelets.

Nanomolar concentration of NSC606985, a camptothecin analog, induces leukemic-cell apoptosis through protein kinase Cδ–dependent mechanisms

Blood ◽  
2005 ◽  
Vol 105 (9) ◽  
pp. 3714-3721 ◽  
Author(s):  
Man-Gen Song ◽  
Shen-Meng Gao ◽  
Ke-Ming Du ◽  
Min Xu ◽  
Yun Yu ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Caspase 3 ◽  
Specific Inhibitor ◽  
Leukemic Cell ◽  
K562 Cells ◽  
Early Event ◽  
Apoptosis Induction ◽  
Proteolytic Activation ◽  
Induced Apoptosis ◽  
Protein Kinase Cδ

AbstractAs a promising new class of anticancer drugs, camptothecins have advanced to the forefront of several areas of therapeutic and developmental chemotherapy. In the present study, we report that NSC606985, a rarely studied camptothecin analog, induces apoptosis in acute myeloid leukemia (AML) cells NB4 and U937 and inhibits the proliferation without cell death in breakpoint cluster region–Abelson murine leukemia (bcr-abl) kinase-carrying leukemic K562 cells. For apoptosis induction or growth arrest, nanomolar concentrations of NSC606985 are sufficient. At such low concentrations, this agent also significantly inhibits the clonogenic activity of hematopoietic progenitors from patients with AML. For apoptosis induction, NSC606985 rapidly induces the proteolytic activation of protein kinase Cδ (PKCδ) with loss of mitochondrial transmembrane potential (ΔΨm) and caspase-3 activation. Cotreatment with rottlerin, a PKCδ-specific inhibitor, completely blocks NSC606985-induced mitochondrial ΔΨm loss and caspase-3 activation, while the inhibition of caspase-3 by z-DEVD-fluoromethyl ketone (Z-DEVD-fmk) only partially attenuates PKCδ activation and apoptosis. These data indicate that NSC606985-induced PKCδ activation is an early event upstream to mitochondrial ΔΨm loss and caspase-3 activation, while activated caspase-3 has an amplifying effect on PKCδ proteolysis. In addition, NSC606985-induced apoptosis by PKCδ also involves caspase-3–independent mechanisms. Taken together, our results suggest that NSC606985 is a potential agent for the treatment of AML.

scholarly journals The essential role of protein kinase Cδ in diabetes-induced neural tube defects

2012 ◽  
Vol 25 (10) ◽  
pp. 2020-2024 ◽  
Author(s):  
Yuanning Cao ◽  
Zhiyong Zhao ◽  
Richard L. Eckert ◽  
E. Albert Reece
Keyword(s):  
Protein Kinase ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Essential Role ◽  
Protein Kinase Cδ

scholarly journals Protein kinase Cδ protects against bile acid apoptosis by suppressing proapoptotic JNK and BIM pathways in human and rat hepatocytes

2014 ◽  
Vol 307 (12) ◽  
pp. G1207-G1215 ◽  
Author(s):  
Cynthia R. L. Webster ◽  
Andrea N. Johnston ◽  
M. Sawkat Anwer
Keyword(s):  
Protein Kinase ◽  
Rat Hepatocytes ◽  
Wild Type ◽  
Akt Phosphorylation ◽  
Akt Activation ◽  
Induced Apoptosis ◽  
Hoechst Staining ◽  
Activate Protein Kinase ◽  
Protein Kinase Cδ

Retained bile acids, which are capable of inducing cell death, activate protein kinase Cδ (PKC-δ) in hepatocytes. In nonhepatic cells, both pro- and antiapoptotic effects of PKC-δ are described. The aim of this study was to determine the role of PKC-δ in glycochenodeoxycholate (GCDC)-induced apoptosis in rat hepatocytes and human HUH7-Na-taurocholate-cotransporting polypeptide (Ntcp) cells. Apoptosis was monitored morphologically by Hoechst staining and biochemically by immunoblotting for caspase 3 cleavage. The role of PKC-δ was evaluated with a PKC activator (phorbol myristate acetate, PMA) and PKC inhibitors (chelerythrine, H-7, or calphostin), PKC-δ knockdown, and wild-type (WT) or constitutively active (CA) PKC-δ. PKC-δ activation was monitored by immunoblotting for PKC-δ Thr505 and Tyr311 phosphorylation or by membrane translocation. JNK and Akt phosphorylation and the amount of total bisindolylmaleimide (BIM) were determined by immunoblotting. GCDC induced the translocation of PKC-δ to the mitochondria and/or plasma membrane in rat hepatocytes and HUH7-Ntcp cells and increased PKC-δ phosphorylation on Thr505, but not on Tyr311, in HUH7-Ntcp cells. GCDC-induced apoptosis was attenuated by PMA and augmented by PKC inhibition in rat hepatocytes. In HUH-Ntcp cells, transfection with CA or WT PKC-δ attenuated GCDC-induced apoptosis, whereas knockdown of PKC-δ increased GCDC-induced apoptosis. PKC-δ silencing increased GCDC-induced JNK phosphorylation, decreased GCDC-induced Akt phosphorylation, and increased expression of BIM. GCDC translocated BIM to the mitochondria in rat hepatocytes, and knockdown of BIM in HUH7-Ntcp cells decreased GCDC-induced apoptosis. Collectively, these results suggest that PKC-δ does not mediate GCDC-induced apoptosis in hepatocytes. Instead PKC-δ activation by GCDC stimulates a cytoprotective pathway that involves JNK inhibition, Akt activation, and downregulation of BIM.

scholarly journals Tyrosine Phosphorylation Regulates the Proteolytic Activation of Protein Kinase Cδ in Dopaminergic Neuronal Cells

2005 ◽  
Vol 280 (31) ◽  
pp. 28721-28730 ◽  
Author(s):  
Siddharth Kaul ◽  
Vellareddy Anantharam ◽  
Yongjie Yang ◽  
Christopher J. Choi ◽  
Arthi Kanthasamy ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Tyrosine Phosphorylation ◽  
Neuronal Cells ◽  
Proteolytic Activation ◽  
Protein Kinase Cδ
Sign in / Sign up

Export Citation Format

Share Document