• Archives of Pharmacal Research
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• v.25 no.6
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• pp.759-769
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• 2002

Mutated forms of ras are found in many human tumors and the rate of incidence is significantly higher in colon and pancreatic cancers. The protein product from the ras oncogene is a small G-protein, $p21^{ras}{\;}(Ras)$ that is known to playa key role in the signal transduction cascade and cell differentiation and proliferation. Mutated Ras is unable to regulate itself and remains constantly activated, leading to uncontrolled cell growth. The function of Ras in signal transduction requires its location near the growth factor receptor at the cell membrane. However, Ras does not have a transmembrane domain. Ras requires farnesylation to increase its hydrophobicity and subsequent plasma membrane association for its transforming activity. This key post-translational modification is catalyzed by the enzyme Ras farnesyltransferase (FTase), which transfers a farnesyl group from farnesylpyrophosphate to the C-terminal cysteine of the Ras protein. The requirement has focused attention on FTase as a target for therapeutic intervention. Selective inhibition of FTase will prevent Ras protein from association with the plasma membrane, leading to a disruption of oncogenic Ras function.

• The Plant Pathology Journal
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• v.26 no.1
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• pp.1-7
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• 2010

Phosphorylation is a major post-translational modification of proteins that regulate diverse signal transduction pathways in eukaryotic cells. 14-3-3 proteins are regulatory proteins that bind to target proteins in a phosphorylation-dependent manner and have been shown to play an important role in plant growth and development, primary metabolism, and signal transduction. Because phosphorylation plays a critical role in signal transduction pathways to trigger plant immunity, involvement of 14-3-3 proteins in plant immunity has been suggested for a long time. Recent studies have provided new evidence to support a role for 14-3-3 proteins in plant immunity. This review will briefly discuss general characteristics of 14-3-3 proteins and their involvement in plant immunity.

• Proceedings of the Botanical Society of Korea Conference
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• 1998.07a
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• pp.83-96
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• 1998

The plant pigment proteins phytochromes are a molecular light sensor or switch for photomorphogenesis involving a variety of growth and developmental responses of plants to red and far-red wavelength light. Underscoring the photomorphogenesis mediated by phytochromes is the light signal transduction at molecular and cellular levels. For example, a number of genes activated by the phytochrome-mediated signal transduction cascade have been identified and characterized, especially in Arabidopsis thaliana. The light sensor/switch function of phytochromes are based on photochromism of the covalently linked tetrapyrrole chromophore between the two photoreversible forms, Pr and Pfr. The photochromism of phytochromes involves photoisomerization of the tetrapyrrole chromophore. The "photosensor" Pr-form ("switch off" conformation) of phytochromes strongly absorbs 660 nm red light, whereas the "switch on" Pfr-conformation preferentially absorbs 730 nm far-red light. The latter is generally considered to be responsible for eliciting transduction cascades of the red light signal for various responses of plants to red light including positive or negative expression of light-responsive genes in plant nuclei and chloroplasts. In this paper, we discuss the structure-function of phytochromes in plant growth and development, with a few examples of biotechnological implications.

• Molecules and Cells
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• v.25 no.3
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• pp.397-406
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• 2008

Computational modeling of signal transduction is currently attracting much attention as it can promote the understanding of complex signal transduction mechanisms. Although several mathematical models have been used to examine signaling pathways, little attention has been given to crosstalk mechanisms. In this study, an attempt was made to develop a computational model for the pathways involving growth-factor-mediated mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3'-kinase/protein kinase B (PI3K/Akt). In addition, the dynamics of the protein activities were analyzed based on a set of kinetic data. The simulation approach integrates the information on several levels and predicts systems behavior. The in-silico analysis conducted revealed that the Raf and Akt pathways act independently.

• The Korean Journal of Zoology
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• v.37 no.1
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• pp.130-136
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• 1994

Although alteration in protein phosphorylation by specific protein kinases is of importance in transducing cellular signals in a variety of neural/endocrine systems, little is known about protein phosphorylation in the hvpothalamus. The present study aims to explore whether activation of the second messenger-dependent protein kinases affects phosphorylation of specific proteins using a cell free phosphorylation system followed by SDS-polvacrylamide gel electrophoresis. Cytoplasmic fractions derived from hvpothalami of immature rats were used as substrates and several activators and/or inhibitors of CAMP-, phosphatidylinositol- and Ca2+-calmodulin-dependent protein kinases were assessed. Many endogenous proteins were extensively phosphorylated and depending on the signal transduction pathways, phosphorvlation profiles were markedly different. The present data indicate that extracellular signals may affect cellular events through protein phosphorylation by second messengers-protein kinases in the rat hypothalamus.

• Tuberculosis and Respiratory Diseases
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• v.43 no.2
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• pp.123-127
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• 1996

Secretion of surfactant phospholipid can be stimulated by a variety of agonists acting via at least three different signal transduction mechanisms. These include the adenylate cyclase system with activation of cAMP-dependent protein kinase; activation of protein kinase C either directly or subsequent to activation of phosphoinositide-specific phospholipase C and generation of diacylglycerols and inositol trisphosphate; and a third mechanism that involves incresed $Ca^{2+}$ levels and a calmodulin-dependent step. ATP stimulates secretion via all three mechanisms. The protein kinase C pathway is also coupled to phopholipase D which, acting on relatively abundant cellular phospholipids, generates diacylglycerols that further activate protein kinase C. Sustained protein kinase C activation can maintain phosphatidylcholine secretion for a prolonged period of time. It is likely that interactions between the different signaling pathways have an important role in the overall physiological regulation of surfactant secretion.

• Genomics & Informatics
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• v.17 no.1
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• pp.8.1-8.10
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• 2019

Alveolar type II cells constitute a small fraction of the total lung cell mass. However, they play an important role in many cellular processes including trans-differentiation into type I cells as well as repair of lung injury in response to toxic chemicals and respiratory pathogens. Transcription factors are the regulatory proteins dynamically modulating DNA structure and gene expression. Transcription factor profiling in microarray datasets revealed that several members of AP1, ATF, $NF-{\kappa}B$, and C/EBP families involved in diverse responses were expressed in mouse lung type II cells. A transcriptional factor signature consisting of Cebpa, Srebf1, Stat3, Klf5, and Elf3 was identified in lung type II cells, Sox9+ pluripotent lung stem cells as well as in mouse lung development. Identification of the transcription factor profile in mouse lung type II cells will serve as a useful resource and facilitate the integrated analysis of signal transduction pathways and specific gene targets in a variety of physiological conditions.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.311.1-311.1
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• 2002

Crystal structure of TRAF6 in complex with TRAF6-binding sites from CD40 was previously determined. The structure revealed a distinct TRAF6-binding groove of CD40. the key structural determinant of interaction. The structural information leads to a proposed TRAF6-binding motif. This allows the identification of TRAF6-binding sequences in the hlRAK protein, whose functional requirement in IL-1 mediated signal transduction is further demonstrated using site-directed mutagenesis. The mutational in IL-1 mediated signal transduction is further dimonstrated using site-directed mutagenesis. The mutational effects of hlRAK on the down-stream NF-${\kappa}$ signaling shows the importance of the TRAF6 interface for signaling by IL-1.

• Molecules and Cells
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• v.19 no.1
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• pp.137-142
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• 2005

We showed recently that ginsenosides inhibit the activity of various types of ion channel. Here we have investigated the role of the carbohydrate component of ginsenoside $Rg_3$ in the inhibition of $Na^+$ channels. The channels were expressed in Xenopus oocytes by injecting cRNAs encoding rat brain Nav1.2 ${\alpha}$ and ${\beta}1$ subunits, and analyzed by the two-electrode voltage clamp technique. Treatment with $Rg_3$ reversibly inhibited the inward $Na^+$ peak current ($I_{Na}$) with an $IC_{50}$ of $32.2{\pm}4.5{\mu}M$, and the inhibition was voltage-dependent. To examine the role of the sugar moiety, we prepared a straight chain form of the second glucose and a conjugate of this glucose with 3-(4-hydroxyphenyl) propionic acid hydrazide (HPPH). Neither derivative inhibited $I_{Na}$. Treatment with the carbohydrate portion of ginsenoside $Rg_3$, sophorose [${\beta}-D-glucopyranosyl$ ($1{\rightarrow}2$)-${\beta}-glucopyranoside$], or the aglycone (protopanaxadiol), on their own or in combination had no effect on $I_{Na}$. These observations indicate that the carbohydrate portion of ginsenoside $Rg_3$ plays an important role in its effect on the $Na^+$ channel.

• Archives of Pharmacal Research
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• v.26 no.10
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• pp.868-873
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• 2003

Ginsenosides, major active ingredients of Panax ginseng, that exhibit various pharmacological and physiological actions are transformed into compound K (CK) or M4 by intestinal microorganisms. CK is a metabolite derived from protopanaxadiol (PD) ginsenosides, whereas M4 is a metabolite derived from protopanaxatriol (PT) ginsenosides. Recent reports shows that ginsenosides might playa role as pro-drugs for these metabolites. In present study, we investigated the effect of bovine serum albumin (BSA), which is one of major binding proteins on various neurotransmitters, hormones, and other pharmacological agents, on ginsenoside $Rg_{2-}$, CK-, or M4-induced regulation of $\alpha3\beta4$ nicotinic acetylcholine (ACh) receptor channel activity expressed in Xenopus oocytes. In the absence of BSA, treatment of ACh elicited inward peak current ($I_{Ach}$) in oocytes expressing $\alpha3\beta4$ nicotinic ACh receptor. Co-treatment of ginsenoside $Rg_2$, CK, or M4 with ACh inhibited IAch in oocytes expressing $\alpha3\beta4$ nicotinic ACh receptor with reversible and dose-dependent manner. In the presence of 1% BSA, treatment of ACh still elicited $I_{Ach}$ in oocytes expressing $\alpha3\beta4$ nicotinic ACh receptor and co-treatment of ginsenoside $Rg_2$ or M4 but not CK with ACh inhibited $I_{Ach}$ in oocytes expressing $\alpha3\beta4$ nicotinic ACh receptor with reversible and dose-dependent manner. These results show that BSA interferes the action of CK rather than M4 on the inhibitory effect of $I_{Ach}$ in oocytes expressing $\alpha3\beta4$ nicotinic ACh receptor and further suggest that BSA exhibits a differential interaction on ginsenoside metabolites.