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Arabidopsis AGC protein kinases IREH1 and IRE3 control root skewing

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Journal of Genetics and Genomics 2019年第5期46卷 259-267页

作者： Xiaozhen Yue Zhiai Guo Teng Shi Lizhen Song Youfa Cheng Key Laboratory of Plant Molecular Physiology Institute of BotanyChinese Academy of SciencesBeijing 100093China University of Chinese Academy of Sciences Beijing 100049China

AGC protein kinases play important roles in plant growth and development.Several AGC kinases in Arabidopsis have been functionally characterized.However,the"AGC Other"subfamily,including IRE,IREH1,IRE3 and IRE4,has not been well understood.Here,we reported that ireh1 mutants displayed a root skewing phenotype,which can be enhanced by ire3 mutation.IREH1 and IRE3 were expressed in roots,consistent with their function in controlling root skewing.The fluorescence intensities of the microtubule marker KNpro:EGFP-MBD were decreased in ireh1,ire3 and ireh1 ire3 mutants compared to wild type.The microtubule arrangements in ireh1 and ireh1 ire3 mutants were also altered.IREH1 physically interacted with IRE3 in vitro and in planta.Thus,our findings demonstrate that IREH1 and IRE3 protein kinases play important roles in controlling root skewing,and maintaining microtubule network in Arabidopsis.

关键词： AGC kinases IREH1 IRE3 Root skewing Microtubule Arabidopsis

The potent roles of salt-inducible kinases(SIKs)in metabolic homeostasis and tumorigenesis

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1141-1155页

作者： Zicheng Sun Qiwei Jiang Jie Li Jianping Guo Institute of Precision Medicine the First Affiliated HospitalSun Yat-Sen UniversityGuangzhouGuangdong 510275China Department of Breast and Thyroid Surgery the First Affiliated HospitalSun Yat-Sen UniversityGuangzhouGuangdong 510275China

Salt-inducible kinases(SIKs)belong to AMP-activated protein kinase(AMPK)family,and functions mainly involve in regulating energy response-related physiological processes,such as gluconeogenesis and lipid metabolism.However,compared with another well-established energy-response kinase AMPK,SIK roles in human diseases,especially in diabetes and tumorigenesis,are rarely investigated.Recently,the pilot roles of SIKs in tumorigenesis have begun to attract more attention due to the finding that the tumor suppressor role of LKB1 in non-small-cell lung cancers(NSCLCs)is unexpectedly mediated by the SIK but not AMPK kinases.Thus,here we tend to comprehensively summarize the emerging upstream regulators,downstream substrates,mouse models,clinical relevance,and candidate inhibitors for SIKs,and shed light on SIKs as the potential therapeutic targets for cancer therapies.

关键词： tumorigenesis homeostasis kinases

Comparative analysis of protein kinases and associated domains between Ascomycota and Basidiomycota

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Journal of Integrative Agriculture 2019年第1期18卷 96-107页

作者： PEI Guo-liang GUO Jun WANG Qin-hu KANG Zhen-sheng State Key Laboratory of Crop Stress Biology for Arid Areas College of Plant ProtectionNorthwest A&F University

Protein kinases play an important role in every aspect of cellular life.In this study,we systemically identified protein kinases from the predicted proteomes of 59 representative fungi from Ascomycota and Basidiomycota.Comparative analysis revealed that fungi from Ascomycota and Basidiomycota differed in the number and variety of protein kinases.Some groups of protein kinases,such as calmodulin/calcium regulated kinases(CMGC) and those with the highest group percentages are the most prevalent protein kinases among all fungal species tested.In contrast,the STE group(homologs of the yeast STE7,STE11 and STE20 genes),was more abundant in Basidiomycetes than in Ascomycetes.Importantly,the distribution of some protein kinase families appeared to be subphylum-specific.The tyrosine kinase-like(TKL) group had a higher protein kinase density in Agaricomycotina fungi.In addition,the distribution of accessory domains,which could have functional implications,demonstrated that usage bias varied between the two phyla.Principal component analysis revealed a divergence between the main functional domains and associated domains in fungi.This study provides novel insights into the variety and expansion of fungal protein kinases between Ascomycota and Basidiomycota.

关键词： protein kinases associated domains Ascomycota Basidiomycota

Targeting receptor tyrosine kinases in gastric cancer

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World Journal of Gastroenterology 2014年第16期20卷 4536-4545页

作者： Asahiro Morishita Jian Gong Tsutomu Masaki Department of Gastroenterology and Neurology Kagawa University School of MedicineKagawa 761-0793Japan

Molecularly targeted therapeutic agents are constantly being developed and have been shown to be effective in various clinical trials.One group of representative targeted oncogenic kinases,the receptor tyrosine kinases(RTKs),has been associated with gastric cancer development.Trastuzumab,an inhibitor of ERBB2,has been approved for the treatment of gastric cancer,although other receptor tyrosine kinases,such as epidermal growth factor receptor,vascular endothelial growth factor,platelet-derived growth factor receptor,c-Met,IGF-1R and fibroblast growth factor receptor 2,are also activated in gastric cancer.The promising results of the trastuzumab clinical trial for gastric cancer resulted in the approval of trastuzumab-based therapy as a first-line treatment for human epidermal growth factor receptor 2-positive patients.On the other hand,the trial examining bevacizumab in combination with conventional chemotherapy did not meet its primary goal of increasing the overall survival time of gastric cancer patients;however,a significantly higher response rate and a longer progression-free survival were observed in the bevacizumab arm of the trial.Other clinical trials,especially phaseⅢtrials that have tested drugs targeting RTKs,such as cetuximab,panitumumab,gefitinib,erlotinib,figitumumab,sorafenib,sunitinib and lapatinib,have shown that these drugs have modest effects against gastric cancer.This review summarizes the recent results from the clinical trials of molecularly targeted drugs and suggests that further improvements in the treatment of advanced gastric cancer can be achieved through the combination of conventional drugs with the new molecularly targeted therapies.

关键词： Receptor tyrosine kinases Gastric cancer Epidermal

Essential kinases and Transcriptional Regulators and their Roles in Autoimmunity

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Essential kinases and Transcriptional Regulators and their R...

Aurora kinases: novel anti-breast cancer targets

第十三届全国免疫学学术大会

作者： Yanan Deng Julie Wang Joseph A Bellanti Bernhard Ryffel Song Guo Zheng Sun Yat-sen University Penn State Univ Georgetown Univ France CNRS

kinases and transcriptional regulators which are fundamental components of cell signaling, they have expressed on many kinds of immune cells, and are involved in the secretion of cytokines, cell proliferation, differentiation and apoptosis, both have important roles in the biological response, Autoimmune diseases include at least 80 diseases, and often controlled by complex genetic and environmental factors. Its pathogenesis is generally due to the breaking of autoimmune tolerance so as to generate an abnormal response to autoantigen. It is a major cause of autoimmune diseases that the balance between self-reactive cells and regulatory cells been broken. Abnormal expression of kinases or transcriptional regulators are often found in aberrant autoimmune cells. These abnormal expressions of kinases or transcriptional regulators can over-activate the function of the self-reactive cells to produce inflammatory factors or down-regulate the activity of regulatory cells, thus producing autoimmune diseases. In this review mainly introduce five kinds of kinase and transcriptional regulator related to autoimmune diseases;namely Janus kinases family(JAK2,TYK2), Fork head box protein 3(FOXP3), the Retinoid-related orphan receptor γ(ROR γ) and T-box expressed in T cells(T-bet). We provide a mechanistic insight into how these kinases and transcriptional regulators affect the immune cells related to autoimmune diseases, as well as the current drug design targeting these kinases and transcriptional regulators to improve the autoimmune disease and inflammatory response, and also discussed the deficiencies in the current research.

关键词： autoimmunity kinases transcriptional factors

来源： cnki会议评论

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Oncology and Translational Medicine 2019年第1期5卷 43-48页

作者： Yiliyaer Yusufu Maimaiti Xinjiang Medical University Graduate School People's Hospital of Xinjiang Uygur Autonomous Region

Aurora kinases regulate multiple steps of mitotic cell division in eukaryotic cells. Overexpression of aurora kinases has been observed in some tumor cells, which suggests that abnormalities in aurora kinases are closely related to tumorigenesis. In additon, aurora kinases are often amplified or overexpressed in breast cancer cells, leading to chromosomal segregation abnormalities and genomic disorder, and thereby activating oncogenic pathways. Novel Aurora A kinase inhibitors are currently being studied in multiple phase I and II studies. In this review, we describe the biological functions and mechanisms of aurora kinases in breast cancer cells and summarize the preclinical findings related to aurora kinases in breast cancer.

关键词： aurora kinases breast cancer inhibitors

“Stop Ne(c)king around”: How interactomics contributes to functionally characterize Nek family kinases

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World Journal of Biological Chemistry 2014年第2期5卷 141-160页

作者： Gabriela Vaz Meirelles Arina Marina Perez Edmárcia Elisa de Souza Ferna Luisa Basei Priscila Ferreira Papa Talita Diniz Melo Hanchuk Vanessa Bomfim Cardoso Jrg Kobarg Laboratório Nacional de Biociências Centro Nacional de Pesquisa em Energia e Materiais Campinas SP 13084-971Brazil Departamento de Bioquímica-Programa de Pós-gradua o em Biologia Funcional e Molecular Instituto de Biologia Universidade Estadual de Campinas Campinas SP 13084-971 Brasil Departamento de Genética Evolu o e Bioagentes-Programa de Pós-gradua o em Genética e Biologia Molecular Instituto de Biologia Universidade Estadual de Campinas1 Campinas SP 13084-97 Brasil

Aside from Polo and Aurora, a third but less studied kinase family involved in mitosis regulation is the never in mitosis-gene A(NIMA)-related kinases(Neks). The founding member of this family is the sole member NIMA of Aspergillus nidulans, which is crucial for the initiation of mitosis in that organism. All 11 human Neks have been functionally assigned to one of the three core functions established for this family in mammals:(1) centrioles/mitosis;(2) primary ciliary function/ciliopathies; and(3) DNA damage response(DDR). Recent findings, especially on Nek 1 and 8, showed however, that several Neks participate in parallel in at least two of these contexts: primary ciliary function and DDR. In the core section of this in-depth review, we report the current detailed functional knowledge on each of the 11 Neks. In the discussion, we return to the cross-connections among Neks and point out how our and other groups' functional and interactomics studies revealed that most Neks interact with protein partners associated with two if not all three of the functional contexts. We then raise the hypothesis that Neks may be the connecting regulatory elements that allow the cell to fine tune and synchronize the cellular events associated with these three core functions. The new and exciting findings on the Nek family open new perspectives and should allow the Neks to finally claim the attention they deserve in the field of kinases and cell cycle biology.

关键词： Cell cycle Mitosis DNA damage response Protein interactions kinases

Group Ⅱ p21-activated kinases as therapeutic targets in gastrointestinal cancer

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World Journal of Gastroenterology 2016年第3期22卷 1224-1235页

作者： Yang-Guang Shao Ke Ning Feng Li Department of Cell Biology Key Laboratory of Cell BiologyMinistry of Public Health and Key Laboratory of Medical Cell BiologyMinistry of EducationChina Medical University

P21-activated kinases(PAKs) are central players in various oncogenic signaling pathways. The six PAK family members are classified into group Ⅰ(PAK1-3) and group Ⅱ(PAK4-6). Focus is currently shifting from group Ⅰ PAKs to group Ⅱ PAKs. Group Ⅱ PAKs play important roles in many fundamental cellular processes, some of which have particular significance in the development and progression of cancer. Because of their important functions, group Ⅱ PAKs have become popular potential drug target candidates. However, few group Ⅱ PAKs inhibitors have been reported, and most do not exhibit satisfactory kinase selectivity and "drug-like" properties. Isoform- and kinase-selective PAK inhibitors remain to be developed. This review describes the biological activities of group Ⅱ PAKs, the importance of group Ⅱ PAKs in the development and progression of gastrointestinal cancer, and smallmolecule inhibitors of group Ⅱ PAKs for the treatment of cancer.

关键词： Group Ⅱ p21-activated kinases Signalingpathway Gastrointestinal cancer PAK4 inhibitor Drugtarget

kinases: Understanding Their Role in HIV Infection

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World Journal of AIDS 2019年第3期9卷 142-160页

作者： William De Martini Roksana Rahman Eduvie Ojegba Emily Jungwirth Jasmine Macias Frederick Ackerly Mia Fowler Jessica Cottrell Tinchun Chu Sulie L. Chang Department of Biological Sciences Seton Hall University South Orange NJ USA Institute of NeuroImmune Pharmacology South Orange NJ USA

Antiviral drugs currently on the market primarily target proteins encoded by specific viruses. The drawback of these drugs is that they lack antiviral mechanisms that account for resistance or viral mutation. Thus, there is a pressing need for researchers to explore and investigate new therapeutic agents with other antiviral strategies. Viruses such as the human immunodeficiency virus (HIV) alter canonical signaling pathways to create a favorable biochemical environment for infectivity. We used Qiagen Ingenuity Pathway Analysis (IPA) software to review the function of several cellular kinases and the resulting perturbed signaling pathways during HIV infection such as NF-κB signaling. These host cellular kinases such as ADK, PKR, MAP3K11 are involved during HIV infection at various stages of the life cycle. Additionally IPA analysis indicated that these modified host cellular kinases are known to have interactions with each other especially AKT1, a serine/threonine kinase involved in multiple pathways. We present a list of cellular host kinases and other proteins that interact with these kinases. This approach to understanding the relationship between HIV infection and kinase activity may introduce new drug targets to arrest HIV infectivity.

关键词： HIV AIDS kinases IPA NF-κB