Defining the combinatorial space of PKC::CARD-CC signal transduction nodes.

Signal transduction typically displays a so-called bow-tie topology: Multiple receptors lead to multiple cellular responses but the signals all pass through a narrow waist of central signaling nodes. One such signaling node for several inflammatory and oncogenic signaling pathways is the CARD-CC/BCL10/MALT1 (CBM) complexes, which get activated by protein kinase C (PKC)-mediated phosphorylation of the caspase activation and recruitment domain (CARD)-coiled-coil domain (CC) component. In humans, there are four CARD-CC family proteins (CARD9, CARD10, CARD11, and CARD14) and 9 true PKC isozymes (α to ι). At this moment, less than a handful of PKC::CARD-CC relationships are known. In order to explore the biologically relevant combinatorial space out of all 36 potential permutations in this two-component signaling event, we made use of CARD10-deficient human embryonic kidney 293T cells for subsequent pairwise cotransfections of all CARD-CC family members and all activated PKCs. Upon analysis of NF-κB-dependent reporter gene expression, we could define specific PKC::CARD-CC relationships. Surprisingly, as many as 21 PKC::CARD-CC functional combinations were identified. CARD10 was responsive to most PKCs, while CARD14 was mainly activated by PKCδ. The CARD11 activation profile was most similar to that of CARD9. We also discovered the existence of mixed protein complexes between different CARD-CC proteins, which was shown to influence their PKC response profile. Finally, multiple PKCs were found to use a common phosphorylation site to activate CARD9, while additional phosphorylation sites contribute to CARD14 activation. Together, these data reveal the combinatorial space of PKC::CARD-CC signal transduction nodes, which will be valuable for future studies on the regulation of CBM signaling.

Protein Sequence Classification Using Natural Vector and Convex Hull Method.

Protein kinase C (PKC) is a superfamily of enzymes, which regulate numerous cellular responses. The specific function of PKC protein family is mainly governed by its individual protein domains. However, existing protein sequence classification methods based on sequence alignment and sequence analysis models focused little on the domain analysis. In this study, we introduce a novel protein kinase classification method that considers both domain sequence similarity and whole sequence similarity to quantify the evolutionary distance from a specific protein to a protein family. Using the natural vector method, we establish a 60-dimensional space, where each protein is uniquely represented by a vector. We also define a convex hull, consisting of the natural vectors corresponding to all members of a protein family. The sequence similarity between a protein and a protein family, therefore, can be quantified as the distance between the protein vector and the protein family convex hull. We have applied this method in a PKC sample library and the results showed a higher accuracy of classification compared with other alignment-free methods.

Evolutionary Analysis of the Lysine-Rich N-terminal Cytoplasmic Domains of the Gastric H+,K+-ATPase and the Na+,K+-ATPase.

The catalytic α-subunits of both the Na+,K+-ATPase and the gastric H+,K+-ATPase possess lysine-rich N-termini which project into the cytoplasm. Due to conflicting experimental results, it is currently unclear whether the N-termini play a role in ion pump function or regulation, and, if they do, by what mechanism. Comparison of the lysine frequencies of the N-termini of both proteins with those of all of their extramembrane domains showed that the N-terminal lysine frequencies are far higher than one would expect simply from exposure to the aqueous solvent. The lysine frequency was found to vary significantly between different vertebrate classes, but this is due predominantly to a change in N-terminal length. As evidenced by a comparison between fish and mammals, an evolutionary trend towards an increase of the length of the N-terminus of the H+,K+-ATPase on going from an ancestral fish to mammals could be identified. This evolutionary trend supports the hypothesis that the N-terminus is important in ion pump function or regulation. In placental mammals, one of the lysines is replaced by serine (Ser-27), which is a target for protein kinase C. In most other animal species, a lysine occupies this position and hence no protein kinase C target is present. Interaction with protein kinase C is thus not the primary role of the lysine-rich N-terminus. The disordered structure of the N-terminus may, via increased flexibility, facilitate interaction with another binding partner, e.g. the surrounding membrane, or help to stabilise particular enzyme conformations via the increased entropy it produces.

Propofol induced diverse and subtype-specific translocation of PKC families.

Propofol is the most commonly used anesthetic. Immunohistochemical studies have reported that propofol translocated protein kinase Cs (PKCs) in cardiomyocyte in a subtype-specific manner; however detailed features of the propofol-induced translocation of PKCs remain unknown. In this study, we performed real-time observation of propofol-induced PKC translocation in SH-SY5Y cells expressing PKCs fused with a fluorescent protein. Propofol unidirectionally translocated γPKC-GFP, a conventional PKC, and ζPKC-GFP, an atypical PKC, to the plasma membrane and nucleus, respectively, whereas the propofol-induced translocation of novel PKCs was diverse and subtype-specific among δPKC, εPKC and ηPKC. The propofol-induced translocation of εPKC-GFP was especially complicated and diverse, that is, 200 µM propofol first translocated εPKC-GFP to the perinuclear region. Thereafter, εPKC was translocated to the nucleus, followed by translocation to the plasma membrane. Analysis using a mutant εPKC in which the C1 domain was deleted demonstrated that the C1b domain of εPKC was indispensable for its translocation to the perinuclear region and plasma membrane, but not for its nuclear translocation. An in vitro kinase assay revealed that propofol increased the activities of the PKCs activities at the concentration that triggered the translocation. These results suggest that propofol could translocate PKCs to their appropriate target sites in a subtype-specific manner and concomitantly activated PKCs at these sites, contributing to its beneficial or adverse effects.

Life on the rocks: Multilocus phylogeography of rock hyrax (Procavia capensis) from southern Africa.

Understanding the role of geography and climatic cycles in determining patterns of biodiversity is important in comparative and evolutionary biology and conservation. We studied the phylogeographic pattern and historical demography of a rock-dwelling small mammal species from southern Africa, the rock hyrax Procavia capensis capensis. Using a multilocus coalescent approach, we assessed the influence of strong habitat dependence and fluctuating regional climates on genetic diversity. We sequenced a mitochondrial gene (cytochrome b) and two nuclear introns (AP5, PRKC1) supplemented with microsatellite genotyping, in order to assess evolutionary processes over multiple temporal scales. In addition, distribution modelling was used to investigate the current and predicted distribution of the species under different climatic scenarios. Collectively, the data reveal a complex history of isolation followed by secondary contact shaping the current intraspecific diversity. The cyt b sequences confirmed the presence of two previously proposed geographically and genetically distinct lineages distributed across the southern African Great Escarpment and north-western mountain ranges. Molecular dating suggests Miocene divergence of the lineages, yet there are no discernible extrinsic barriers to gene flow. The nuclear markers reveal incomplete lineage sorting or ongoing mixing of the two lineages. Although the microsatellite data lend some support to the presence of two subpopulations, there is weak structuring within and between lineages. These data indicate the presence of gene flow from the northern into the southern parts of the southern African sub-region likely following the secondary contact. The distribution modelling predictably reveal the species' preference for rocky areas, with stable refugia through time in the northern mountain ranges, the Great Escarpment, as well as restricted areas of the Northern Cape Province and the Cape Fold Mountains of South Africa. Different microclimatic variables appear to determine the distributional range of the species. Despite strong habitat preference, the micro-habitat offered by rocky crevices and unique life history traits likely promoted the adaptability of P. capensis, resulting in the widespread distribution and persistence of the species over a long evolutionary period. Spatio-temporal comparison of the evolutionary histories of other co-distributed species across the rocky landscapes of southern Africa will improve our understanding of the regional patterns of biodiversity and local endemism.

An information-based network approach for protein classification.

Protein classification is one of the critical problems in bioinformatics. Early studies used geometric distances and polygenetic-tree to classify proteins. These methods use binary trees to present protein classification. In this paper, we propose a new protein classification method, whereby theories of information and networks are used to classify the multivariate relationships of proteins. In this study, protein universe is modeled as an undirected network, where proteins are classified according to their connections. Our method is unsupervised, multivariate, and alignment-free. It can be applied to the classification of both protein sequences and structures. Nine examples are used to demonstrate the efficiency of our new method.

Characterization of nitric oxide signaling pathways in the mouse retina.

Nitric oxide (NO) is a gaseous neuromodulator with physiological functions in every retinal cell type. NO is synthesized by several nitric oxide synthases (NOS) and often functions through its second messenger, cyclic guanosine monophosphate (cGMP), and protein kinase G (PKG). This study combined NO imaging, immunocytochemistry, biochemistry, and molecular biology to localize NO and its downstream signaling pathways in the mouse retina. Neuronal NOS (nNOS) was localized primarily in puncta in the inner plexiform layer, in amacrine cells, and in somata in the ganglion cell layer. Endothelial NOS was in blood vessels. Light-stimulated NO production imaged with diaminofluorescein was present in somata in the inner nuclear layer and in synaptic boutons in the inner plexiform layer. The downstream target of NO, soluble guanylate cyclase (sGC), was in somata in the inner and outer nuclear layers and in both plexiform layers. Cyclic GMP immunocytochemistry was used functionally to localize sGC that was activated by an NO donor in amacrine, bipolar, and ganglion cells. Cyclic GMP-dependent protein kinase (PKG) Iα was found in bipolar cells, ganglion cells, and both plexiform layers, whereas PKG II was found in the outer plexiform layer, amacrine cells, and somata in the ganglion cell layer. This study shows that the NO/cGMP/PKG signaling pathway is functional and widely distributed in specific cell types in the outer and inner mouse retina. A better understanding of these signaling pathways in normal retina will provide a firm basis for targeting their roles in retinal pathology.

Identification of differentially expressed microRNAs and their PKC-isoform specific gene network prediction during hypoxic pre-conditioning and focal cerebral ischemia of mice.

We previously reported the involvement of conventional protein kinase C (cPKC) ßII, γ, novel PKC (nPKC) ε and their interacting proteins in hypoxic pre-conditioning (HPC)-induced neuroprotection. In this study, the large-scale miRNA microarrays and bioinformatics analysis were used to determine the differentially expressed miRNAs and their PKC-isoform specific gene network in mouse brain after HPC and 6 h middle cerebral artery occlusion (MCAO). We found 4 up-regulated and 13 down-regulated miRNAs in the cortex of HPC mice, 26 increased and 39 decreased gene expressions of miRNAs in the peri-infarct region of 6 h MCAO mice, and 11 up-regulated and 22 down-regulated miRNAs in the peri-infarct region of HPC and 6 h MCAO mice. Based on Diff Score, 19 differentially expressed miRNAs were identified in HPC and 6 h MCAO mouse brain. Then the miRNA-gene-network of 19 specified miRNAs target genes of cPKCßII, γ and nPKCε-interacting protein was predicted by using bioinformatics analysis of genome databases. Furthermore, the down-regulated miR-615-3p during HPC had a detrimental effect on the oxygen-glucose deprivation (OGD)-induced N2A cell injury. These results suggested that the identified 19 miRNAs, notably miR-615-3p, might target these genes of cPKCßII, γ and nPKCε-interacting proteins involved in HPC-induced neuroprotection.

PKC isoenzymes in equine platelets and stimulus induced activation.

Protein kinase C (PKC) is an important regulator of platelet activation and different isoenzymes can play positive and negative regulatory roles. The PKC isoenzymes expressed in equine platelets have not been documented but pharmacological inhibition has suggested a role for PKC delta (δ) in modulating responsiveness to platelet activating factor (PAF) (Brooks et al., 2009). Here the PKC isoenzyme profile in equine platelets has been characterised and PKCδ activation by PAF investigated. Platelet lysates were probed by Western blotting using a panel of antibodies against individual PKC isoenzymes. PKCδ and eight other isoenzymes were identified, namely classical PKCs alpha (α), beta (ß), (both ßI and ßII) and gamma (γ), the novel PKCs epsilon (ɛ), eta (η) and theta (θ) and atypical PKC zeta (ζ). Having shown PKCδ to be present, a method was developed to measure PAF-induced isoenzyme translocation by preparing cytosolic and membrane fractions from digitonin permeabilised platelets. Phorbol 12-myristate 13-acetate (PMA) was shown to cause translocation of PKCδ to the membrane within 5s. PAF also caused PKCδ translocation although the response occurred more slowly; a significant, 7.6 ± 1.2 fold, increase in band density compared to unstimulated platelets was observed at 15 min; p=0.036, n=3. These data support a role for PKCδ in regulating PAF-induced functional responses in equine platelets.

The involvement of specific PKC isoenzymes in phorbol ester-mediated regulation of steroidogenic acute regulatory protein expression and steroid synthesis in mouse Leydig cells.

Protein kinase C (PKC) is a multigene family of serine/threonine kinases. PKC is involved in regulating adrenal and gonadal steroidogenesis; however, the functional relevance of the different PKC isoenzymes remains obscure. In this study, we demonstrate that MA-10 mouse Leydig tumor cells express several PKC isoforms to varying levels and that the activation of PKC signaling, by phorbol 12-myristate 13-acetate (PMA) elevated the expression and phosphorylation of PKCα, -δ, -ε, and -µ/protein kinase D (PKD). These responses coincided with the expression of the steroidogenic acute regulatory (StAR) protein and progesterone synthesis. Targeted silencing of PKCα, δ, and ε and PKD, using small interfering RNAs, resulted in deceases in basal and PMA-mediated StAR and steroid levels and demonstrated the importance of PKD in steroidogenesis. PKD was capable of controlling PMA and cAMP/PKA-mediated synergism involved in the steroidogenic response. Further studies pointed out that the regulatory events effected by PKD are associated with cAMP response element-binding protein (CREB) and c-Jun/c-Fos-mediated transcription of the StAR gene. Chromatin immunoprecipitation studies revealed that the activation of phosphorylated CREB, c-Jun, and c-Fos by PMA was correlated with in vivo protein-DNA interactions and the recruitment of CREB-binding protein, whereas knockdown of PKD suppressed the association of these factors with the StAR promoter. Ectopic expression of CREB-binding protein enhanced the trans-activation potential of CREB and c-Jun/c-Fos in StAR gene expression. Using EMSA, a -83/-67-bp region of the StAR promoter was shown to bind PKD-transfected MA-10 nuclear extract in a PMA-responsive manner, targeting CREB and c-Jun/c-Fos proteins. These findings provide evidence for the presence of multiple PKC isoforms and demonstrate the molecular events by which selective isozymes, especially PKD, influence PMA/PKC signaling involved in the regulation of the steroidogenic machinery in mouse Leydig cells.

Protein kinase C regulates neurite outgrowth in spinal cord neurons.

OBJECTIVE: The functional roles of protein kinase C (PKC) in the neurite outgrowth and nerve regeneration remain controversial. The present study was aimed to investigate the role of PKC in neurite outgrowth, by studying their regulatory effects on neurite elongation in spinal cord neurons in vitro. METHODS: The anterior-horn neurons of spinal cord from embryonic day 14 (E14) Sprague-Dawley (SD) rats were dissociated, purified and cultured in the serum-containing medium. The ratio of membrane-PKC (mPKC) activity to cytoplasm-PKC (cPKC) activity (m/c-PKC) was studied at different time points during culture. RESULTS: Between 3-11 d of culture, the change of m/c-PKC activity ratio and PKC-betaII expression in the neurite were both significantly correlated with neurite outgrowth (r=0.95, P< 0.01; r=0.73, P< 0.01, respectively). Moreover, PMA, an activator of PKC, induced a dramatic elevation in the m/c-PKC activity ratio, accompanied with the increase in neurite length (r=0.99, P< 0.01). In contrast, GF 109203X, an inhibitor of PKC, significantly inhibited neurite elongation, which could not be reversed by PMA. CONCLUSION: PKC activity may be important in regulating neurite outgrowth in spinal cord neurons, and betaII isoform of PKC probably plays a major role in this process.

[The function of protein kinase C in myocardial fibrosis].

Myocardial fibrosis is the common results of the development of a variety of heart diseases which leads to extracellular matrix protein metabolic disorders and causes cardiac remodeling owing to cardiac fibroblasts proliferation, eventually results in malignant arrhythmia, heart failure, and even the occurrence of sudden cardiac death. Effective inhibition of myocardial remodeling could prevent the occurrence of sudden death. To know the protein kinase C (PKC) effective mechanism of regulation on myocardial fibrosis, a new therapeutic target for reversing myocardial remodeling might be provided.

Protein kinase D1: a new component in TLR9 signaling.

Protein kinase D1 (PKD1) is expressed ubiquitously and regulates diverse cellular processes such as oxidative stress, gene expression, cell survival, and vesicle trafficking. However, the presence and function of PKD1 in monocytic cells are currently unknown. In this study, we provide evidence that PKD1 is involved in TLR9 signaling in macrophages. Class B-type CpG DNA (CpG-B DNA) induced activation of PKD1 via a pathway that is dependent on endosomal pH, TLR9, MyD88, and IL-1R-associated kinase 1 in macrophages. Upon CpG-B DNA stimulation, PKD1 interacted with the TLR9/MyD88/IL-1R-associated kinase/TNFR-associated factor 6 complex. Knockdown of PKD1 revealed that PKD1 is required for activation of NF-kappaB and MAPKs, and subsequent expression of cytokines in response to CpG-B DNA. Our findings identify PKD1 as a key signaling modulator in TLR9-mediated macrophage activation.

Selective binding of phorbol esters and diacylglycerol by individual C1 domains of the PKD family.

The PKD (protein kinase D) family are novel DAG (diacylglycerol) receptors. The twin C1 domains of PKD, designated C1a and C1b, have been shown to bind DAG or phorbol esters. However, their ligand-binding activities and selectivities have not been fully characterized. Here, binding activities of isolated C1a, C1b and intact C1a-C1b domains to DAG and phorbol esters were analysed. The isolated C1b domains of PKD isoforms bind [(3)H]PDBu ([20-(3)H]phorbol 12, 13-dibutyrate) with similar high affinities, while they exhibit weaker affinities towards a synthetic DAG analogue, DOG (1,2-dioctanoyl-sn-glycerol), as compared to the control. Mutating a conserved lysine residue at position 22 to tryptophan in C1b of PKD3 fully restores its affinity to DOG, indicating that this residue accounts for its weaker affinity to DOG. In contrast, the non-consensus residues in the isolated C1a domain of PKD mainly contribute to maintaining the protein's structural fold, since converting these residues in C1a of PKD3 to those in PKD1 or PKD2 drastically reduces the maximal number of active receptors, while only minimally impacting ligand-binding activities. Moreover, ligand-binding activities of C1a and C1b are sensitive to the structural context in an intact C1a-C1b domain and exhibit unique patterns of ligand selectivity. C1a and C1b in the intact C1a-C1b of PKD1 are opposite in selectivity for PDBu and DOG. In contrast, C1a of PKD3 exhibits 48-fold higher affinity to DOG as compared to C1b, although both domains bind PDBu with equivalent affinities. Accordingly, mutating C1a of a full-length PKD3-GFP greatly reduces DOG-induced plasma membrane translocation, but does not affect that induced by PMA. In summary, individual C1 domains of PKD isoforms differ in ligand-binding activity and selectivity, implying isoform-selective regulation of PKD by phorbol esters and DAG.

Targeting the protein kinase C family: are we there yet?

Protein kinase C (PKC) comprises a family of serine/threonine kinases that are involved in the transduction of signals for cell proliferation, differentiation, apoptosis and angiogenesis. Unsurprisingly, disruption of PKC regulation is implicated in tumorigenesis and drug resistance. PKC function is complex in this context owing to the differing roles of individual isozymes within the cell and across tumour types. Therapeutically targeting PKC isozymes is not new; however, with many of the early PKC inhibitor cytotoxic drug combinations being discarded at the phase II level, and recent phase III studies in non-small-cell lung cancer proving negative, what's going wrong?

Protein kinase C isoforms from Giardia duodenalis: identification and functional characterization of a beta-like molecule during encystment.

Protein kinase C (PKC) is a family of serine/threonine kinases that regulate many different cellular processes such as cell growth and differentiation in eukaryotic cells. Using specific polyclonal antibodies raised against mammalian PKC isoforms, it was demonstrated here for the first time that Giardia duodenalis expresses several PKC isoforms (beta, delta, epsilon, theta and zeta). All PKC isoforms detected showed changes in their expression pattern during encystment induction. In addition, selective PKC inhibitors blocked the encystment in a dose-dependent manner, suggesting that PKC isozymes may play important roles during this differentiation process. We have characterized here the only conventional-type PKC member found so far in Giardia, which showed an increased expression and changes in its intracellular localization pattern during cyst formation. The purified protein obtained by chromatography on DEAE-cellulose followed by size-exclusion chromatography, displayed in vitro kinase activity using histone HI-IIIS as substrate, which was dependent on cofactors required by conventional PKCs, i.e., phospholipids and calcium. An open reading frame in the Giardia Genome Database that encodes a homolog of PKCbeta catalytic domain was identified and cloned. The expressed recombinant protein was also recognized by a mammalian anti-PKCbeta antibody and was referred as giardial PKCbeta on the basis of all these experimental evidence.

PKC isotype functions in T lymphocytes.

The main function of mature T cells is to recognize and respond to foreign antigens by a complex activation process involving differentiation of the resting cell to a proliferating lymphoblast actively secreting immunoregulatory lymphokines or displaying targeted cytotoxicity, ultimately leading to recruitment of other cell types and initiation of an effective immune response. In order to understand the physiology and pathophysiology of T lymphocytes, it is necessary to decode the biochemical processes that integrate signals from antigen, cytokine, integrin and death receptors. The principal upon which our work is based is to explore and identify gene products of distinct members of the AGC family of protein serine/threonine kinases as key players mediating cell growth regulation. Given the established important role of PKC theta as regulator of T cell fate and knowing that several other PKC isotypes are also expressed in T cells at a high level, we now summarize the physiological and non-redundant functions of PKC alpha, beta, delta, epsilon, zeta and theta isotypes in T cells. This review describes the current knowledge of the physiological and non-redundant functions of the PKC gene products in T cells.

Signaling cascades in radiation-induced apoptosis: roles of protein kinase C in the apoptosis regulation.

Apoptosis is a biologic mechanism for eliminating damaged cells from the cell population. Apoptosis is known to be induced by irradiation and can prevent the development of disease states such as carcinogenesis or abnormal tissue formation. On the other hand, if the mechanism is properly controlled, radiotherapy can be used to kill cancer cells more efficiently. Radiation-induced apoptosis is regulated by the balance between cellular anti-apoptotic and (pro-)apoptotic signals. Many regulators of radiation-induced apoptosis have been identified and analyzed. Protein kinase C (PKC) is a family of serine/threonine kinases and one of the regulators in radiation-induced apoptosis. PKC has some subtypes, each of whose functions has been analyzed in radiation-induced signaling cascades. It has been demonstrated that each of PKC subtypes has distinct functions in radiation-induced apoptosis. Moreover, some participants in PKC-related signaling cascades have been identified in radiation-induced apoptosis. Interestingly, PKC-related signaling cascades have been found to be regulated in part by ATM (the gene that is mutated in the human genetic disorder ataxia telangiectasia). ATM is a protein related to cell-cycle checkpoints and cell radiosensitivity, and it also regulates radiation-induced apoptosis. This article reviews recent developments in the understanding of radiation-induced apoptosis, focusing on PKC functions, and the relationship with ATM.

Effect of protein kinase C inhibitors on porcine oocyte activation.

The effect of protein kinase C (PKC) inhibitors on porcine oocyte activation by calcium ionophore A23187 was studied. Calcium ionophore applied in a 50 microM concentration for 10 min induced activation in 74% of oocytes matured in vitro. When the ionophore-treated oocytes were exposed to the effect of bisindolylmaleimide I, which inhibits calcium-dependent PKC isotypes (PKC-alpha, -beta(I), -beta(II), -gamma,) and calcium-independent PKC isotypes (PKC-delta, -epsilon), the portion of activated oocytes decreased (at a concentration of 100 nM, 2% of the oocytes were activated). Go6976, the inhibitor of calcium-dependent PKC isotypes PKC-alpha, -beta(I) did not prevent the action of the oocytes treated with calcium ionophore in concentrations from 1 to 100 microM. The inhibitor of PKC-beta(I) and beta(II) isotypes, hispidin, in a concentration of 2 microM-2 mM, was not effective either. The inhibitor of PKC-delta isotype, rottlerin, suppressed activation of the oocytes by calcium ionophore (no oocyte was activated at 10 microM concentration). The PKC-delta isotype in matured porcine oocytes, studied by Western blot analysis, appeared as non-truncated PKC-delta of 77.5 kDa molecular weight, on the one hand, and as truncated PKC-delta, which was present in the form of a doublet of approximately 62.5 and 68 kDa molecular weight, on the other hand. On the basis of these results, it can be supposed that PKC participates in the regulation of processes associated with oocyte activation. Calcium-dependent PKC-alpha, -beta isotypes do not seem to play any significant role in calcium activation. The activation seems to depend on the activity of the calcium-independent PKC-delta isoform.

[The role of protein kinase C in intracellular regulation mechanisms of adrenocortical cell function in norm and in pathology].

The data on the role of protein kinase C enzymes family in regulation of biochemical processes in adrenocortical cells and other types of steroid-producing cells were analyzed. The involvement of these protein kinase reactions in signal transduction of main regulators of adrenocortical function--ACTH, angiotensin II and potassium ions was considered. Data about interactions and transregulation influences between different secondary messenger systems, which mediate intracellular signal transduction of agonists and provide functional activity of adrenocortical cells are discussed. The participation of protein kinase C is shown in changing of the steroidogenic genes expression. The role of protein kinase C isoforms in tumorogenesis is described.