• Journal of Plant Biotechnology
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• 제42권4호
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• pp.277-283
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• 2015

Plant genome analyses, including Arabidopsis thaliana showed a large gene family of plant receptor kinases with various extracellular ligand-binding domain. Now intensively studies to understand physiological and cellular functions for higher plant receptor kinases in diverse and complex biological processes including plant growth, development, ligands perception including steroid hormone and plant-microbe interactions. Brassinosteroids (BRs) as a one of well know steroid hormone are plant growth hormones that control biomass accumulation and also tolerance to many biotic and abiotic stress conditions and hence are of relevance to agriculture. BRI1 receptor kinase, which is localized in plasma membrane in the cell sense BRs and it bind to a receptor protein known as BRASSINOSTEROID INSENSITIVE 1 (BRI1). Recently, we reported that BRI1 and its co-receptor, BRI1-ASSOCIATED KINASE (BAK1) autophosphorylated on tyrosine residue (s) in vitro and in vivo and thus are dual-specificity kinases. Other plant receptor kinases are also phosphorylated on tyrosine residue (s). Post-translational modifications (PTMs) can be studied by altering the residue modified by directed mutagenesis to mimic the modified state or to prevent the modification. These approaches are useful to not only characterize the regulatory role of a given modification, but may also provide opportunities for plant improvement.

• Journal of Plant Biotechnology
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• 제45권4호
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• pp.315-321
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• 2018

Molecular and functional characterization of proteins and their levels is of great interest in understanding the mechanism of diverse cellular processes. In this study, we report on the convenient Escherichia coli-based protein expression system that allows recombinant of soluble proteins expression and cytosolic domain of membrane-localised kinases, followed by the detection of autophosphorylation activity in protein kinases. This approach is applied to regulatory proteins of Arabidopsis thaliana, including 14-3-3, calmodulin, calcium-dependent protein kinase, TERMINAL FLOWER 1(TFL1), FLOWERING LOCUS T (FT), receptor-like cytoplasmic kinase and cytoplasmic domain of leucine-rich repeat-receptor like kinase proteins. Our Western blot analysis which uses phospho-specific antibodies showed that five putative LRR-RLKs and two putative RLCKs have autophosphorylation activity in vitro on threonine and/or tyrosine residue(s), suggesting their potential role in signal transduction pathways. Our findings were also discussed in the broader context of recombinant expression and biochemical analysis of soluble and membrane-localised receptor kinases in microbial systems.

• Archives of Pharmacal Research
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• 제21권5호
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• pp.487-495
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• 1998

Gorwth factors such as TGF-beta, PDGF and FGF are thought to play important roles in wound healing. However, thier biological activity and signal transduction during wound repair remain poorly understood. Growth factors are often ligands for receptor tyrosine kinase and receptor serine/threonine kinases. With recent advances in signal transduction by receptor kinases, we are beginning to understand the underlying mechanism of how growth factors may regulate cutaneous wound repair. In this paper, we will describe the pharmacological effects of growth factors on wound healing, and dscuss the potential underlying signaing mechanisms. thus, we hope to provide the basis for designing more specific therapeutics for wound healing in the near future.

• Natural Product Sciences
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• 제27권2호
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• pp.134-139
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• 2021

A new cipadesin limonoid, i.e. 3-epi-cipadonoid C (1), and a new tirucallane triterpene, i.e. hispidol B 3-palmitate (3), have been isolated from the seeds and fruit peels extract of Sandoricum koetjape, respectively. Along with these compounds the known limonoid, cipaferen G (2), and two pentacyclic triterpenes, bryonolic (4) and bryononic (5) acids, were also isolated. The strucrures of the new compounds were elucidated by the analysis of NMR and mass spectral data. Compounds 1 - 5 were evaluated as the inhibitor of receptor tyrosine kinases (EGFR, Epidermal Growth Factor Receptor; HER2, HER4, Human Epidermal growth factor Receptor 2, -4; IGFR, Insulin-like Growth Factor Receptor; InsR, Insulin Receptor; KDR, Kinase insert Domain Receptor; PDGFRα, and PDGFRβ, Platelet-Derived Growth Factor Receptor-α and -β). The results showed only 1 and 3 that have weak activity against InsR.

• Molecules and Cells
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• 제28권3호
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• pp.195-200
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• 2009

Protein tyrosine kinases (PTKs) play a central role in the modulation of a wide variety of cellular events such as differentiation, proliferation and metabolism, and their unregulated activation can lead to various diseases including cancer and diabetes. PTKs represent a diverse family of proteins including both receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (NRTKs). Due to the diversity and important cellular roles of PTKs, accurate classification methods are required to better understand and differentiate different PTKs. In addition, PTKs have become important targets for drugs, providing a further need to develop novel methods to accurately classify this set of important biological molecules. Here, we introduce a novel statistical model for the classification of PTKs that is based on their structural features. The approach allows for both the recognition of PTKs and the classification of RTKs into their subfamilies. This novel approach had an overall accuracy of 98.5% for the identification of PTKs, and 99.3% for the classification of RTKs.

• The Korean Journal of Physiology and Pharmacology
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• 제6권3호
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• pp.139-142
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• 2002

To examine intracellular signaling of human $S1P_3\;(hS1P_3),$ a sphingosine 1-phosphate (S1P) receptor in plasma membrane, $hS1P_3$ DNA was transfected into RH7777 rat hepatoma cell line, and the inhibition of forskolin-induced cAMP accumulation and activation of MAP kinases by S1P were tested. In $hS1P_3$ transformants, S1P inhibited forskolin-induced activation of adenylyl cyclase activity by about 80% and activated MAP kinases in dose-dependent and pertussis-toxin (PTX) sensitive manners. In oocytes expressing $hS1P_3$ receptor, S1P evoked $Cl^-$ conductance. These data suggested that PTX-sensitive G proteins are involved in $hS1P_3-mediated$ signaling, especially the positive action of S1P in cell proliferation. The potential advantages of rat hepatoma cells for the research of sphingosine 1-phosphate receptor are discussed.

• Biomolecules & Therapeutics
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• 제19권4호
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• pp.390-397
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• 2011

G protein-coupled receptor kinases (GRKs) and ${\beta}$-arrestins have been known as regulators of G protein-coupled receptors. However, it has been recently reported that GRKs and ${\beta}$-arrestins mediate receptor-mediated cellular responses in a G proteinin-dependent manner. In this scheme, GRKs work as a mediator or a scaffold protein. Among 7 members of the GRK family (GRK1-GRK7), GRK2 is the most extensively studied in vitro and in vivo. GRK2 is involved in cellular migration, insulin signaling, and cardiovascular disease. GRK6 in concert with ${\beta}$-arrestin 2 mediates chemoattractant-stimulated chemotaxis of T and B lymphocytes. GRK5 shuttles between the cytosol and nucleus, and regulates the activities of transcription factors. GRK3 and GRK4 do not seem to have striking effects on cellular responses other than receptor regulation. GRK1 and GRK7 play specific roles in regulation of rhodopsin function. In this review, these newly discovered functions of GRKs are briefly described.

• 한국임상수의학회지
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• 제26권5호
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• pp.429-432
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• 2009

Cadherin-catenin 복합체의 파괴는 ${\beta}$-catenin 단백질의 발현 위치 이상(세포내 이동)을 유발하며, 일부 receptor tyrosine kinase (RTK)의 활성화가 cadherin-catenin 복합체의 파괴를 유발할 수 있다. 본 연구에서는 ${\beta}$-catenin의 발현 위치 이상을 나타낸 개 피부 흑색종 조직 18개에서 MET/RON RTKs의 발현양을 평가하였다. 실험 결과 총 28%의 종양조직에서 MET/RON RTKs의 발현증가가 관찰되었다. 이 결과는 개 피부 흑색종에서 MET/RON RTKs의 발현증가가 ${\beta}$-catenin의 위치이상에 부분적으로 관여할 가능성을 제시한다.

• BMB Reports
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• 제43권5호
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• pp.311-318
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• 2010

This review explored the mechanism of breast carcinoma progression by focusing on integrins and receptor tyrosine kinases (or growth factor receptors). While the primary role of integrins was previously thought to be solely as mediators of adhesive interactions between cells and extracellular matrices, it is now believed that integrins also regulate signaling pathways that control cancer cell growth, survival, and invasion. A large body of evidence suggests that the cooperation between integrin and receptor tyrosine kinase signaling regulates certain signaling functions that are important for cancer progression. Recent developments on the crosstalk between integrins and receptor tyrosine kinases, and its implication in mammary tumor progression, are discussed.

• Biomolecules & Therapeutics
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• 제31권4호
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• pp.359-369
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• 2023

Dependence receptors are a group of receptor proteins with shared characteristics of transducing two different signals within cells. They can transduce a positive signal of survival and differentiation in the presence of ligands. On the other hand, dependence receptors can transduce an apoptosis signal in the absence of ligands. The function of these receptors depends on the availability of their ligands. Several receptor tyrosine kinases (RTKs) have been reported as dependence receptors. When cells undergo apoptosis by dependence receptors, the intracellular domain of some RTKs is cleaved by the caspases. Among the RTKs that belong to dependence receptors, we focused on eight RTKs (RET, HER2, MET, ALK, TrkC, EphA4, EphB3, and c-KIT) that are cleaved by caspases. In this review, we describe the features of the receptors, their cleavage sites, and the fate of the cleaved products, as well as recent implications on them being used as potential therapeutics for cancer treatment.