• BMB Reports
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• 제55권2호
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• pp.87-91
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• 2022

Aurora kinase is a family of serine/threonine kinases intimately associated with mitotic progression and the development of human cancers. Studies have shown that aurora kinases are important for the protein kinase C (PKC)-induced invasion of colon cancer cells. Recent studies have shown that aurora kinase A promotes distant metastasis by inducing epithelial-to-mesenchymal transition (EMT) in colon cancer cells. However, the role of aurora kinase A in colon cancer metastasis remains unclear. In this study, we investigated the effects of aurora kinase A on PKC-induced cell invasion, migration, and EMT in human SW480 colon cancer cells. Treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) changed the expression levels of EMT markers, increasing α-SMA, vimentin, and MMP-9 expression and decreasing E-cadherin expression, with changes in cell morphology. TPA treatment induced EMT in a PKC-dependent manner. Moreover, the inhibition of aurora kinase A by siRNAs and inhibitors (reversine and VX-680) suppressed TPA-induced cell invasion, migration, and EMT in SW480 human colon cells. Inhibition of aurora kinase A blocked TPA-induced vimentin and MMP-9 expression, and decreased E-cadherin expression. Furthermore, the knockdown of aurora kinase A decreased the transcriptional activity of NF-κB and AP-1 in PKC-stimulated SW480 cells. These findings indicate that aurora kinase A induces migration and invasion by inducing EMT in SW480 colon cancer cells. To the best of our knowledge, this is the first study that showed aurora kinase A is a key molecule in PKC-induced metastasis in colon cancer cells.

• 생물정신의학
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• 제6권1호
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• pp.67-73
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• 1999

The cAMP-dependent protein kinase(PKA) is an intracellular enzyme with serine-threonine kinase activity that plays a key role in cell growth, differentiation, and apoptosis in eukaryotes. In order to understand the PKA signal transduction pathway regulating cell life cycle and identify its role, we focused on the characterization of up-/down-regulated genes by PKA using the differential display polymerase chain reaction. Seven differentially expressed sequence tags(DEST) have been obtained. Among these DESTs, 2 DESTs were homologous to the sequence of genes from BLAST search result. KC1-5 DEST that was up-regulated in A123.7 cells was highly corresponded to mouse apoptosis-related gene(MA-3) or mouse mRNA for topoisomerase inhibitor suppressed(TIS). MA-3 was induced in various types of apoptosis, specially in NGF-deprived apoptotic PC12 cells. TIS was down-regulated in the RVC lymphoma cells incubated with topoisomerase inhibitor that induces DNA strand breakages. PG1-1 DEST that was highly expressed in PC12 cells was corresponded to transposon Tn10 3'-end. Tnansposon Tn10 was up-regulated in differentiated myeloblastic ML-1 cells by 12-O-tetradecanoylphorbol-13-acetate. This study illuminates that MA-3/TIS was down-regulated by PKA activity, and transposon Tn10 was up-regulated by it.

• BMB Reports
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• 제38권6호
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• pp.639-645
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• 2005

Protein kinase C (PKC) isozymes, a family of serine-threonine kinases, are important regulators of cell proliferation and malignant transformation. Phorbol esters, the prototype PKC activators, cause PKC translocation to the plasma membrane in prostate cancer cells, and trigger an apoptotic response. Studies in recent years have determined that each member of the PKC family exerts different effects on apoptotic or survival pathways. $PKC{\delta}$, one of the novel PKCs, is a key player of the apoptotic response via the activation of the p38 MAPK pathway. Studies using RNAi revealed that depletion of $PKC{\delta}$ totally abolishes the apoptotic effect of the phorbol ester PMA. Activation of the classical $PKC{\alpha}$ promotes the dephosphorylation and inactivation of the survival kinase Akt. Studies have assigned a pro-survival role to $PKC{\varepsilon}$, but the function of this PKC isozyme remains controversial. Recently, it has been determined that the PKC apoptotic effect in androgen-dependent prostate cancer cells is mediated by the autocrine secretion of death factors. $PKC{\delta}$ stimulates the release of $TNF{\alpha}$ from the plasma membrane, and blockade of $TNF{\alpha}$ secretion or $TNF{\alpha}$ receptors abrogates the apoptotic response of PMA. Molecular analysis indicates the requirement of the extrinsic apoptotic cascade via the activation of death receptors and caspase-8. Dissecting the pathways downstream of PKC isozymes represents a major challenge to understanding the molecular basis of phorbol ester-induced apoptosis.

• Journal of Microbiology and Biotechnology
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• 제20권1호
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• pp.208-216
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• 2010

Fusarium verticillioides is an important pathogen of maize, being responsible for ear rots, stalk rots, and seedling blight worldwide. During the past decade, F. verticillioides has caused several severe epidemics of maize seedling blight in many areas of China, which lead to significant losses. In order to understand the molecular mechanisms regulating fungal development and pathogenicity in this pathogen, we isolated and characterized the gene fpk1 (GenBank Accession No. EF405959) encoding a homolog of the cAMP-dependent protein kinase catalytic subunit, which included a 1,854-bp DNA sequence from ATG to TAA, with a 1,680-bp coding region, and three introns (lengths: 66 bp, 54 bp, and 54 bp), and the predicated protein precursor had 559 aa. The mutant ${\Delta}fpk1$, which was disrupted of the fpkl gene, showed reduced vegetative growth, fewer and shorter aerial mycelia, strongly impaired conidiation, and reduced spore germination rate. After germinating, the fresh hypha was stubby and lacking of branch. When inoculated in susceptible maize varieties, the infection of the mutant ${\Delta}fpk1$ was delayed and the infection efficiency was reduced compared with that of the wild-type strain. AU this indicated that gene fpk1 participated in hyphal growth, conidiophore production, spore germination, and virulence in F. verticillioides.

• BMB Reports
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• 제47권11호
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• pp.631-636
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• 2014

Aurora-A is a centrosome-localized serine/threonine kinase that is overexpressed in multiple human cancers. We previously reported an intramolecular inhibitory regulation of Aurora-A between its N-terminal regulatory domain (Nt, amino acids [aa] 1-128) and the C-terminal catalytic domain (Cd, aa 129-403). Here, we demonstrate that although both Aurora-A mutants (AurA-K250G and AurA-D294G/Y295G) lacked interactions between the Nt and Cd, they also failed to interact with Ajuba, an essential activator of Aurora-A, leading to loss of kinase activity. Additionally, overexpression of either of the mutants resulted in centrosome amplification and mitotic spindle formation defects. Both mutants were also able to cause G2/M arrest and apoptosis. These results indicate that both K250 and D294/Y295 are critical for direct interaction between Aurora-A and Ajuba and the function of the Aurora-A complex in cell cycle progression.

• Asian Pacific Journal of Cancer Prevention
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• 제17권12호
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• pp.5087-5094
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• 2016

mTOR, the mammalian target of rapamycin, is a conserved serine/threonine kinase which belongs to the phosphatidyl-linositol kinase-related kinase (PIKK) family. It has two complexes called mTORC1 and mTORC2. It is well established that mTOR plays important roles in cell growth, proliferation and differentiation. Over-activation of the mTOR pathway is considered to have a relationship with the development of many types of diseases, including polycystic ovary syndrome (PCOS) and ovarian cancer (OC). mTOR pathway inhibitors, such as rapamycin and its derivatives, can directly or indirectly treat or relieve the symptoms of patients suffering from PCOS or OC. Moreover, mTOR inhibitors in combination with other chemical-molecular agents may have extraordinary efficacy. This paper will discuss links between mTOR signaling and PCOS and OC, and explore the mechanisms of mTOR inhibitors in treating these two diseases, with conclusions regarding the most effective therapeutic approaches.

• Molecules and Cells
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• 제26권1호
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• pp.100-105
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• 2008

Glycogen synthase kinase $3{\beta}$ (GSK $3{\beta}$) is a serine/threonine kinase that phosphorylates substrates such as ${\beta}$-catenin and is involved in a variety of biological processes, including embryonic development, metabolism, tumorigenesis, and cell death. Here, we present evidence that human GSK $3{\beta}$ is associated with Fe65, which has the characteristics of an adaptor protein, possessing a WW domain, and two phosphotyrosine interaction domains, PID1 and PID2. The GSK $3{\beta}$ catalytic domain also contains a putative WW domain binding motif ($^{371}PPLA^{374}$), and we observed, using a pull down approach and co-immunoprecipitation, that it interacts physically with Fe65 via this motif. In addition, we detected co-localization of GSK $3{\beta}$ and Fe65 by confocal microscopy, and this co-localization was disrupted by mutation of the putative WW domain binding motif of GSK $3{\beta}$. Finally, in transient transfection assays interaction of GSK $3{\beta}$ (wt) with Fe65 induced substantial cell apoptosis, whereas interaction with the GSK $3{\beta}$ AALA mutant ($^{371}AALA^{374}$) did not, and we noted that phosphorylation of the Tyr 216 residue of the GSK $3{\beta}$ AALA mutant was significantly reduced compared to that of GSK $3{\beta}$ wild type. Thus, our observations indicate that GSK $3{\beta}$ binds to Fe65 through its $^{371}PPLA^{374}$ motif and that this interaction regulates apoptosis and phosphorylation of Tyr 216 of GSK $3{\beta}$.

• 동의생리병리학회지
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• 제20권5호
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• pp.1315-1320
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• 2006

The root and rhizomes of Nardostachys chinensis belonging to the family Valerianaceae has been used for medicinal therapy in Korean traditional medicine. The parts have been especially used to elicit stomachic and sedative effects. Our previous studies reported that the water extract of N. chinensis has induced granulocytic differentiation inhuman promyelocytic leukemia (HL-60) cells. The Mitogen-activated protein kinases (MAPKs) are serine/threonine kinases involved in the regulation of various cellular responses, such as cell proliferation, differentiation and apoptosis. In this study, we investigated the signaling pathways on the HL-60 cell differentiation induced by N. chinensis. Activation of extracellular signal-regulated kinase (ERK) increased time-dependently in differentiation of HL-60 cells induced by N. chinersis. Activation of p38 increased slightly at 24 h after N. chinensis treatment, but activation of c-jun N-terminal kinase (JNK) was unaffected. Inhibitor of ERK (PD98059) significantly reduced NBT reduction activity induced by N. chinensis in HL-60 cells. In contrast, p38 inhibitor (SB203580) did not inhibit the cell differentiation. These results indicated that activaiton of ERK may De involved in HL-60 cell differentiation induced by N. chinensis.

• 생명과학회지
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• 제22권3호
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• pp.428-436
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• 2012

단백질 인산화는 세포의 활동을 조절하는 보편적인 과정이다. 브라시노스테로이드(brassinostreoid)에 의해 매개되는 신호전달은 브라시노스테로이드에 의해 활성화된 세포막상의 protein kinase 로부터 인산화되어 있는 전사인자들을 탈인산화하는 연속적인 인산화/탈인산화 과정이다. 브라시노스테로이드에 의해 매개되는 신호전달의 연구는 인산화에 관여하는 kinase 기질상의 아미노산을 밝히고, 그와 관련된 돌연변이체의 표현형을 알아봄으로써 급속하게 발전하였다. BRI1과 BAK1의 자기인산화(autophosphorylation), 상호인산화(transphosphorylation), 타이로신 인산화(tyrosine phosphorylation)를 밝힘으로써 그들의 조절작용을 식물의 생리학적, 발생학적 과정을 더 이해할 수 있는 장이 열렸다. 브라시노스테로이드에 의한 인산화는 수용체에 의해 매개되는 세포 내 함입(endocytosis)과 그에 뒤따르는 수용체의 파괴현상에서도 볼 수 있다. 인산화/탈인산화 과정에 관련하여 브라시노스테로이드에 의해 매개되는 신호전달은 더 연구할 여지가 많이 남아 있다. 이 총설은 단백질의 인산화/탈인산화 과정을 통한 브라시노스테로이드의 신호전달 연구의 최근 상황을 기술하였다.

• Journal of Photoscience
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• 제9권2호
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• pp.335-337
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• 2002

Blue light (BL) induces stomatal opening through activation of H$^{+}$ pump, which creates electrical gradient across the plasma membrane for $K^{+}$ uptake into guard cells. The pump is the plasma membrane H$^{+}$ -ATPase and is activated via phosphorylation of the C-terminus with concomitant binding of the 14-3-3 protein. The opening is initiated by the perception of BL through phototropin (phot), which are recently identified as BL receptors in stomatal guard cells. In this study, we provide the biochemical evidence for phots as BL receptors in stomatal guard cells. vfphot was phosphorylated reversibly by BL, and phosphorylation levels of vfphot increased earlier than those of the plasma membrane W-ATPase. BL-dependent phosphorylations of vfphot and H$^{+}$-ATPase showed similar fluence dependency. Staurosporin, an inhibitor of serine/threonine protein kinase, and diphenyleneiodonium chloride (DPI), an inhibitor of flavoprotein, inhibited BL-dependent phosphorylations of vfphot and H$^{+}$ -ATPase. These results indicate that vfphot acts as a BL-receptor mediating stomatal opening.l opening.