scholarly journals Protein kinase C in cellular transformation: a valid target for therapy?

2014 ◽  
Vol 42 (6) ◽  
pp. 1556-1562 ◽  
Author(s):  
Anuradha Tarafdar ◽  
Alison M. Michie
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
B Cell ◽  
Critical Role ◽  
Prognostic Significance ◽  
Family Members ◽  
Cellular Transformation ◽  
Signalling Pathways ◽  
Kinase C ◽  
Pkc Isoforms

The protein kinase C (PKC) family of serine/threonine protein kinases share structural homology, while exhibiting substantial functional diversity. PKC isoforms are ubiquitously expressed in tissues which makes it difficult to define roles for individual isoforms, with complexity compounded by the finding that PKC isoforms can co-operate with or antagonize other PKC family members. A number of studies suggest the involvement of PKC family members in regulating leukaemic cell survival and proliferation. Chronic lymphocytic leukaemia (CLL), the most common leukaemia in the Western world, exhibits dysregulated expression of PKC isoforms, with recent reports indicating that PKCβ and δ play a critical role in B-cell development, due to their ability to link the B-cell receptor (BCR) with downstream signalling pathways. Given the prognostic significance of the BCR in CLL, inhibition of these BCR/PKC-mediated signalling pathways is of therapeutic relevance. The present review discusses the emerging role of PKC isoforms in the pathophysiology of CLL and assesses approaches that have been undertaken to modulate PKC activity.

Functional implications of assigned, assumed and assembled PKC structures

2014 ◽  
Vol 42 (1) ◽  
pp. 35-41 ◽  
Author(s):  
Mark Linch ◽  
Philippe Riou ◽  
Jeroen Claus ◽  
Angus J. Cameron ◽  
Julien de Naurois ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Family Members ◽  
Pharmacological Intervention ◽  
Signalling Pathways ◽  
Membrane Targeting ◽  
Domain Structures ◽  
Kinase C ◽  
Functional Implications ◽  
Pkc Protein Kinase C

The empirical derivation of PKC (protein kinase C) domain structures and those modelled by homology or imputed from protein behaviour have been extraordinarily valuable both in the elucidation of PKC pathway mechanisms and in the general lessons that extrapolate to other signalling pathways. For PKC family members, there are many domain/subdomain structures and models, covering all of the known domains, variably present in this family of protein serine/threonine kinases (C1, C2, PB1, HR1, kinase domains). In addition to these structures, there are a limited number of complexes defined, including the structure of the PKCε V3–14-3-3 complex. In the context of structure-driven insights into PKC pathways, there are several broadly applicable principles and mechanisms relevant to the operation of and intervention in signalling pathways. These principles have an impact in unexpected ways, from the regulation of membrane targeting, through strategies for pharmacological intervention, to biomarkers.

scholarly journals Activation of protein kinase C family members by the novel polyphosphoinositides PtdIns-3,4-P2 and PtdIns-3,4,5-P3.

1994 ◽  
Vol 269 (51) ◽  
pp. 32358-32367
Author(s):  
A Toker ◽  
M Meyer ◽  
K K Reddy ◽  
J R Falck ◽  
R Aneja ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Family Members ◽  
The Novel ◽  
Kinase C

scholarly journals Prognostic impact of protein kinase C β II expression in R-CHOP-treated diffuse large B-cell lymphoma patients

2010 ◽  
Vol 23 (5) ◽  
pp. 686-693 ◽  
Author(s):  
Sari Riihijärvi ◽  
Satu Koivula ◽  
Heidi Nyman ◽  
Karin Rydström ◽  
Mats Jerkeman ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Kinase C ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Relationship between Protein kinase C isoforms, Telomerase and Alpha- fetoprotein through PI3K/AKT/mTOR pathway in Hepatocellular carcinoma

MedPharmRes ◽  
2021 ◽  
Vol 5 (4) ◽  
pp. 12-26
Author(s):  
Rita Ammoury ◽  
Roula Tahtouh ◽  
Nadine Mahfouz ◽  
Raia Doumit ◽  
Charbel Khalil ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Telomerase Activity ◽  
Mtor Pathway ◽  
Alpha Fetoprotein ◽  
Mrna Levels ◽  
Htert Expression ◽  
Kinase C ◽  
Pkc Isoforms

Protein kinase C (PKC) family has been an alluring objective for new cancer drug discovery. It has been reported to regulate telomerase in several cancer types. Our team had previously used telomerase to elucidate alpha-fetoprotein (AFP) modulation in hepatocellular carcinoma (HCC). The aim of this study was to investigate the interrelationships among PKC isoforms, telomerase and AFP in HCC. PKCα and PKCδ were the most expressed isoforms in HepG2/C3A, PLC/PRF/5, SNU-387 and SKOV-3 cells. Following the upregulation of AFP using pCMV3-AFP and the human telomerase reverse transcriptase (hTERT) using a construct expressing a wild-type hTERT, and after their inhibition with all-trans retinoic acid and hTERT siRNA each respectively, we found that the expression of PKCα, PKCβI, PKCβII and PKCδ was affected by the variation of AFP and hTERT mRNA levels. An increase in AFP expression and secretion was observed after gene silencing of PKCα, PKCβ, PKCδ, and PKCε in HepG2/C3A. A similar pattern was observed in transfected PLC/PRF/5 cells, however PKCδ isoform silencing decreased AFP expression. Furthermore, telomerase activity was quantified using quantitative telomeric repeat amplification protocol. The variations in hTERT expression and telomerase activity were similar to those of AFP. Further investigation showed that PKC isoforms regulate AFP and hTERT expression levels through PI3K/AKT/mTOR pathway in HepG2/C3A and PLC/PRF/5 cells. Thus, these results show for the first time a possible interrelationship that links PKC isoforms to both AFP and hTERT via PI3K/AKT/mTOR pathway in HCC.

Protein kinase C-α and the regulation of diverse cell responses

2017 ◽  
Vol 8 (3-4) ◽  
pp. 143-153 ◽  
Author(s):  
Rishi Kant Singh ◽  
Sanjay Kumar ◽  
Pramod Kumar Gautam ◽  
Munendra Singh Tomar ◽  
Praveen Kumar Verma ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cellular Localization ◽  
Cellular Transformation ◽  
Cell Types ◽  
Adapter Proteins ◽  
Cellular Functions ◽  
Cell Responses ◽  
Kinase C ◽  
Cellular Compartments

AbstractProtein kinase C (PKC) comprises a family of lipid-sensitive enzymes that have been involved in a broad range of cellular functions. PKC-α is a member of classical PKC with ubiquitous expression and different cellular localization. This unique PKC isoform is activated by various signals which evoke lipid hydrolysis, after activation it interacts with various adapter proteins and is localized to specific cellular compartments where it is devised to work. The universal expression and activation by various stimuli make it a perfect player in uncountable cellular functions including differentiation, proliferation, apoptosis, cellular transformation, motility, adhesion and so on. However, these functions are not intrinsic properties of PKC-α, but depend on cell types and conditions. The activities of PKC-α are managed by the various pharmacological activators/inhibitors and antisense oligonucleotides. The aim of this review is to elaborate the structural feature, and provide an insight into the mechanism of PKC-α activation and regulation of its key biological functions in different cellular compartments to develop an effective pharmacological approach to regulate the PKC-α signal array.

Association of protein kinase C-δ with the B cell antigen receptor complex

2007 ◽  
Vol 19 (4) ◽  
pp. 715-722 ◽  
Author(s):  
Catrin Pracht ◽  
Susana Minguet ◽  
Michael Leitges ◽  
Michael Reth ◽  
Michael Huber
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
B Cell ◽  
Antigen Receptor ◽  
B Cell Antigen Receptor ◽  
Receptor Complex ◽  
Cell Antigen Receptor ◽  
Cell Antigen ◽  
Kinase C

scholarly journals Modeled microgravity-induced protein kinase C isoform expression in human lymphocytes

2004 ◽  
Vol 96 (6) ◽  
pp. 2028-2033 ◽  
Author(s):  
A. Sundaresan ◽  
D. Risin ◽  
N. R. Pellis
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Type I Collagen ◽  
Human Lymphocytes ◽  
Receptor Interaction ◽  
Type I ◽  
Modeled Microgravity ◽  
Calcium Dependent ◽  
Kinase C ◽  
Pkc Isoforms

In long-term space travel, the crew is exposed to microgravity and radiation that invoke potential hazards to the immune system. T cell activation is a critical step in the immune response. Receptor-mediated signaling is inhibited in both microgravity and modeled microgravity (MMG) as reflected by diminished DNA synthesis in peripheral blood lymphocytes and their locomotion through gelled type I collagen. Direct activation of protein kinase C (PKC) bypassing cell surface events using the phorbol ester PMA rescues MMG-inhibited lymphocyte activation and locomotion, whereas the calcium ionophore ionomycin had no rescue effect. Thus calcium-independent PKC isoforms may be affected in MMG-induced locomotion inhibition and rescue. Both calcium-dependent isoforms and calcium-independent PKC isoforms were investigated to assess their expression in lymphocytes in 1 g and MMG culture. Human lymphocytes were cultured and harvested at 24, 48, 72, and 96 h, and serial samples were assessed for locomotion by using type I collagen and expression of PKC isoforms. Expression of PKC-α, -δ, and -ϵ was assessed by RT-PCR, flow cytometry, and immunoblotting. Results indicated that PKC isoforms δ and ϵ were downregulated by >50% at the transcriptional and translational levels in MMG-cultured lymphocytes compared with 1- g controls. Events upstream of PKC, such as phosphorylation of phospholipase Cγ in MMG, revealed accumulation of inactive enzyme. Depressed calcium-independent PKC isoforms may be a consequence of an upstream lesion in the signal transduction pathway. The differential response among calcium-dependent and calcium-independent isoforms may actually result from MMG intrusion events earlier than PKC, but after ligand-receptor interaction.

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