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protein kinase inhibitors affect spermatogenic functions and blood testis barrier remodelling:A scoping review

Asian pacific Journal of Reproduction 2023年第3期12卷 97-108页

作者： Oyovwi Mega Obukohwo Onome Bright Oghenetega Falajiki Yewande Faith Emojevwe Victor Rotu Arientare Rume Joseph Gregory Uchechukwu Oyeleke Abiodun Abioye Department of Physiology Faculty of Basic Medical SciencesAdeleke UniversityEdeOsun StateNigeria Department of Physiology School of Basic Medical ScienceBabcock UniversityIllisan-RomoOgun StateNigeria Department of Physiology University of Medical SciencesOndo StateNigeria Department of Physiology University of IbadanIbadanOyo StateNigeria Department of Medical Laboratory Science Adeleke UniversityEdeOsun StateNigeria Department of Physiology Federal University Oye-EkitiNigeria

Objective:To identify the role of protein kinase in male reproduction in animal models and human spermatogenic ***:This study assessed the protein kinase of male reproduction in animal models and human using different reviewed paper indexed in PubMed,Science Direct,EBSCO,Scopus,Cochrane Library,Sage Journals,and Google *** were charted based on author,year of publication published between 1893 and 2023,country,purpose,data collection,key findings,and research focus/***:The MAPK pathway contributed to the growth,maturation,and functionality of male germ *** also found out that certain influencing factors categorized into hormonal/non hormonal factors and chemotoxicant,as well as heat stress expressed an inhibitory mechanism on protein kinase,thus affecting spermatogenic functions and maintenance/remodeling of the blood testis barrier,as well as the physiology of the Sertoli cells necessary for nutritional support of ***,activating protein kinases pathway like the mTOR pathway as well as increased expression of peroxiredoxin-4 and L-carnitine mediated protein kinases may be useful for treating or managing male reproductive ***:protein kinase plays an important role in spermatogenic functions and blood testis remodeling in animal and *** assessment provides essential information that can guide treatment strategies aimed at improving male reproductive *** together,these recent advances highlight a future therapeutic intervention in assessing male reproductive *** might also be possible to look at potential targets for male contraceptives in the MAPK pathway.

关键词： Spermatogenesis protein kinase Inhibitors Sertoli cells Capacitation mTOR

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The Putative Ser/Thr protein kinase Gene GmAAPKfrom Soybean is Regulated by Abiotic Stress

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Journal of Integrative Plant Biology 2006年第3期48卷 327-333页

作者： Guang-Zuo Luo Yong-Jun Wang Jin-Song Zhang Zong-Ming Xie Jun-Yi Gai Shou-Yi Chen State Key Laboratory of Plant Genomics Institute of Genetics and Developmental Biology the Chinese Academy of Sciences Beijing 100101 China National Center for Soybean Improvement Nanjing Agricultural University Nanjing 210095 China Graduate School of the Chinese Academy of Sciences Beijing 100039 China

Osmotic stress caused by dehydration or high-salt conditions poses a major environmental challenge for plant growth and development. Many studies have shown that protein kinases are important regulators during osmotic stress in plants. In the present study, we describe GmAAPK, a soybean （Glycine max （L.） Merr.） gene coding for a putative serine/threonine protein kinase （abscisic acid （ABA）-activated protein kinase （AAPK））. The cDNA for GmAAPKis 1 409 bp long and contains a single long open reading frame representing a complete coding region of 359 amino acids. GmAAPKwas mapped onto the D1a＋Q linkage group. Its transcripts are expressed in all tissues, but at high levels in the cotyledon. GmAAPKmRNA was induced by polyethylene glycol, ABA, Ca^2＋ and Na^＋, but not cold （4℃） treatments in soybean leaves. The results suggest that GmAAPK may participate in the regulatory process during osmotic stresses in soybean.

关键词： abiotic stress protein kinase SnRK2 soybean.

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CIPK9: a calcium sensor-interacting protein kinase required for low-potassium tolerance in Arabidopsis

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Cell Research 2007年第5期17卷 411-421页

作者： Girdhar K Pandey Yong Hwa Cheong Beom-Gi Kim John J Grant Legong Li Department of Plant and Microbial Biology University of CaliforniaBerkeley CA 94720USA

Potassium is one of the major macro-nutrients essential for a number of cellular processes in plants. Low potassiumlevel in the soil represents a limiting factor for crop production. Recent studies have identified potassium transporters thatare involved in potassium acquisition, and some of them are critical for potassium nutrition under low potassium condi-tions. However, little is understood on the molecular components involved in low potassium signaling and responses. Wereport here the identification of a calcineurin B-like protein-interacting protein kinase （CIPK9） as a critical regulator oflow potassium response in Arabidopsis. The CIPK9 gene was responsive to abiotic stress conditions, and its transcriptwas inducible in both roots and shoots by potassium deprivation. Disruption of CIPK9 function rendered the mutantplants hypersensitive to low potassium media. Further analysis indicated that K+uptake and content were not affected inthe mutant plants, implying CIPK9 in the regulation of potassium utilization or sensing processes.

关键词： calcium calcineurin-B like protein protein kinase potassium nutrition signal transduction

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Molecular Modeling of Interactions of the Benzolactam-V8 Modulators with the Cys2 Domain of protein kinase Cδ

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Chinese Journal of Chemistry 2007年第10期25卷 1434-1438页

作者：黄莉莉马大为夏宗芗 State Key Laboratory of Bioorganic and Natural Products Chemistry Shanghai Institute of Organic Chemistry Chinese Academy of Sciences Shanghai 200032 China

Molecular modeling of interactions of four 7- or 8-substituted benzolactam-V8 （BLV） molecules with the cys2 activator-binding domain of protein kinase C （PKCδ） was carried out using molecular docking program Autodock. The docked models reveal that the hydroxymethyl group at the C（5） atom of the eight-membered ring of each BLV is bound at the bottom of the binding groove of the cys2 domain of PKCδ The BLV molecules make hydrogen bonds and hydrophobic interactions with PKCδ, which are similar to those in the crystal structure of the cys2 domain of PKCδ in complex with phorbol 13-acetate. BLV-1 does not contain a long side chain that is hydrophobic and necessary for membrane insertion, so that it would not be a potent modulator of PKCδ. The other three BLV molecules have long side chains substituted at C（7） or C（8） atoms, and it was predicted, based on the docking results, that they had the PKCδ-binding affinity in the order of BLV-2〉BLV-4〉BLV-3, and BLV-2 would be a potent activator of PKCδ.

关键词： protein kinase regulatory domain modulator benzolactam molecular docking protein-ligand interaction hydrogen bond hydrophobic interaction PKCδ-binding affinity

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An Autophosphorylation Site of the protein kinase SOS2 Is Important for Salt Tolerance in Arabidopsis

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Molecular Plant 2009年第1期2卷 183-190页

作者： Hiroaki Fujii Jian-Kang Zhu Department of Botany and Plant Sciences 2150 Batchelor Hall University of California Riverside CA 92521 USA

The protein kinase SOS2 （Salt Overly Sensitive 2） is essential for salt-stress signaling and tolerance in Arabidopsis. SOS2 is known to be activated by calcium-SOS3 and by phosphorylation at its activation loop. SOS2 is autophosphorylated in vitro, but the autophosphorylation site and its role in salt tolerance are not known. In this study, we identified an autophosphorylation site in SOS2 and analyzed its role in the responses of Arabidopsis to salt stress. Mass spectrometry analysis showed that Ser 228 of SOS2 is autophosphorylated. When this site was mutated to Ala, the autophosphorylation rate of SOS2 decreased. The substrate phosphorylation by the mutated SOS2 was also less than that by the wild-type SOS2. In contrast, changing Ser228 to Asp to mimic the autophosphorylation enhanced substrate phosphorylation by SOS2. Complementation tests in a sos2 mutant showed that the S228A but not the $228D mutation partially disrupted the function of SOS2 in salt tolerance. We also show that activation loop phosphorylation at Thr168 and autophosphorylation at Ser228 cannot substitute for each other, suggesting that both are required for salt tolerance. Our results indicate that Ser 228 of SOS2 is autophosphorylated and that this autophosphorylation is important for SOS2 function under salt stress.

关键词： SOS2 autophosphorylation salt tolerance protein kinase Arabidopsis

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EFFECT　OF　PHORBOL　ESTER　ON　cAMP－DEPENDENT　protein　kinase　ACTIVITY　IN　CARDIOMYOCYTES

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Chinese Medical Sciences Journal 1995年第4期10卷 191-194页

作者：周文华肖殿模郑超强王小鲁张俊保 Department of Pathophysiology Institute of Basic Medical Science Beijing.

Cardiomyocytes isolated from neonatal rats were treated with phorboll 2-myristatel 3-acetate (PMA ) ranging from 10(-11)to 10-7 mol/L for 20 min, causing cytosol protein kinase A (PKA) activity to decrease while particulate PKA activity increase in a concentration-dependent manner. The change of PKA activity induced by PMA was abolished completely by pretreatment of polymyxin B or depletion of protein kinase C (PKC). Type II PKA activity in particulate fraction was enhanced remarkably, while that of type I PKA was not altered when the cells were treated with 100 nmol/L PMA. The results suggested that subcellular distribution and activity of PKA in cardiomyocytes may be regulated by PKC.

关键词： protein kinase phorbol ester cardiomyocytes

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Existence and Characteristics of Tonoplast-bound protein kinase in the Tip Cell of Maize Root

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Acta Botanica Sinica 2002年第6期44卷 661-666页

作者：陈硕陈珈王学臣中国农业大学生物学院

For understanding the function of tonoplast protein in plant cell signal pathway, we have identified an integral protein kinase activity from the highly purified tonoplast isolated from maize ( Zea mays L.) root by a new nonradioactive method in which a color labeled peptide was used as substrate. The protein kinase was Ca 2+ _dependent and CaM and phosphatidylserine_independent, like the calmodulin_like domain protein kinase (CDPK) in many plants. The optimal pH value and Ca 2+ concentration were 6.5 and 10 μmol/L, respectively. According to the optimal pH value and the effect of detergent, it could be inferred that the active site of this protein kinase is oriented toward the cytoplasm. Zn 2+ had no obvious effect on its activity, indicating that this protein kinase has no zinc_finger domain that exists in some mammalian protein kinases. At the same time, when tonoplast proteins were prephosphorylated in the presence of Ca 2+ and ATP, both the ATP_hydrolysis and the proton_transport activity of vacuolar H +_ATPase were stimulated. This stimulation could be reversed by an alkaline_phosphatase. These results indicate that a Ca 2+ _dependent protein kinase was located in the tonoplast, and a Ca 2+ _dependent phosphorylation, probably caused by this kinase, activated the vacuolar H +_ATPase activity. These results are helpful for further research on the function of CDPK in the course of signal transduction in plants.

关键词： protein kinase phosphorylation H +_ATPase tonoplast maize

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Molecular Cloning and Characterization of a Serine/Threonine protein kinase Gene from Triticum aestivum

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Acta Botanica Sinica 2002年第3期44卷 325-328页

作者：牛吉山于玲马正强陈佩度刘大钧南京农业大学农业部作物细胞遗传重点实验室

To isolate genes related to resistance to Erysiphe graminis DC. ex Merat f. sp. tritici Em. Marchal in wheat (Triticum aestivum L.), differential display analysis was conducted for mRNA extracted from the seedlings of the wheat-Haynaldia villosa 6VS/6AL translocation line 92RI37 that contains the powdery mildew resistance gene Pm21. A full-length cDNA named TaPK1 was isolated. BLAST analysis revealed that it was significantly homologous to Glycine max (L.) Merr. protein kinase (GmPK6) cDNA. TaPK1 encodes a 416 amino acid long polypeptide, which belongs to serine/threonine protein kinase family, also has tyrosine kinase specificity. TaPK1 is a novel protein kinase from wheat.

关键词： wheat powdery mildew protein kinase

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Pharmacophore approaches in protein kinase inhibitors design

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World Journal of Pharmacology 2014年第4期3卷 162-173页

作者： Sergiy A Starosyla Galyna P Volynets Volodymyr G Bdzhola Andriy G Golub Sergiy M Yarmoluk Department of Medicinal Chemistry Institute of Molecular Biology and Genetics NAS of Ukraine03680 Kyiv Ukraine OTAVA Ltd. 400 Applewood Crescent Unit 100 Vaughan Ontario L4K0C3 Canada

protein kinases constitute a superfamily of therapeutic targets for a number of human and animal diseases that include more than 500 members accordingly to sequencing data of the human genome. The well characterized nature of protein kinases makes them excellent targets for drug development. Pharmacophore approaches have become one of the major tools in the area of drug discovery. Application of pharmacophore modeling approaches allows reducing of expensive overall cost associated with drug development project. Pharmacophore models are important functional groups of atoms in the proper spatial position for interaction with target protein. Various ligand-based and structurebased methods have been developed for pharmacophore model generation. Despite the successes in pharmacophore models generation these approaches have not reached their full capacity in application for drug discovery. In the following review, we summarize the published data on pharmacophore models for inhibitorsof tyrosine protein kinases(EGFR, HER2, VEGFR, JAK2, JAK3, Syk, ZAP-70, Tie2) and inhibitors of serine/threonine kinases(Clk, Dyrk, Chk1, IKK2, CDK1, CDK2, PLK, JNK3, GSK3, m TOR, p38 MAPK, PKB). Here, we have described the achievements of pharmacophore modeling for protein kinase inhibitors, which provide key points for further application of generated pharmacophore hypotheses in virtual screening, de novo design and lead optimization.

关键词： protein kinase Inhibitor Pharmacophore model Receptor-based method Ligand-based method

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Oscillatory change of SR-protein kinase activities during oocyte maturation meiosis in fish

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Progress in Natural Science:Materials International 2000年第2期 69-73页

作者：杨仲安曹丹桂建芳 China Chinese Academy of Sciences Institute of Hydrobiology State Key Laboratory of Freshwater Ecology and Biotechnology Wuhan 430072

The SR-protein kinase activity was analyzed and the cytological changes were observed during oocyte maturation in bisexual transparent color crucian carp ( Carassius auratus color variety) . The results revealed that the SR-protein kinase activity was sensitive to the artificially induced spawning hormones, and the change of oscillatory activity was similar to that of the maturation-promoting factor (MPF) kinase that regulates meiotic cell cycle in fish.

关键词： protein kinase SRPK1 oocyte maturation meiosis kinase activity assay.

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