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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 *** AGC kinases in Arabidopsis have been functionally ***,the"AGC Other"subfamily,including IRE,IREH1,IRE3 and IRE4,has not been well ***,we reported that ireh1 mutants displayed a root skewing phenotype,which can be enhanced by ire3 ***1 and IRE3 were expressed in roots,consistent with their function in controlling root *** fluorescence intensities of the microtubule marker KNpro:EGFP-MBD were decreased in ireh1,ire3 and ireh1 ire3 mutants compared to wild *** microtubule arrangements in ireh1 and ireh1 ire3 mutants were also ***1 physically interacted with IRE3 in vitro and in ***,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 ***,compared with another well-established energy-response kinase AMPK,SIK roles in human diseases,especially in diabetes and tumorigenesis,are rarely ***,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 ***,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

Targeting autophagy-related protein kinases for potential therapeutic purpose

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Acta Pharmaceutica Sinica B 2020年第4期10卷 569-581页

作者： Honggang Xiang Jifa Zhang Congcong Lin Lan Zhang Bo Liu Liang Ouyang State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan UniversityCollaborative Innovation Center for BiotherapyChengdu 610041China School of Life Science and Engineering Southwest Jiaotong UniversityChengdu 610031China State Key Laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjing 210023China

Autophagy,defined as a scavenging process of protein aggregates and damaged organelles mediated by lysosomes,plays a significant role in the quality control of macromolecules and *** protein kinases are integral to the autophagy process,it is critically important to understand the role of kinases in autophagic *** present,intervention of autophagic processes by small-molecule modulators targeting specific kinases has becoming a reasonable and prevalent strategy for treating several varieties of human disease,especially *** this review,we describe the role of some autophagy-related kinase targets and kinase-mediated phosphorylation mechanisms in autophagy *** also summarize the small-molecule kinase inhibitors/activators of these targets,highlighting the opportunities of these new therapeutic agents.

关键词： Autophagy Protein kinases Autophagy-related kinase Phosphorylation Small-molecule kinase inhibitors/activators Human disease therapy

Ubiquitination-mediated regulation of receptor-like kinases in symbiosis and immunity

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Molecular Plant 2024年第9期17卷 1335-1337页

作者： David Landry Benoit Lefebvre Laboratory of Plant-Microbe-Environment Interactions(LIPME) Universite de ToulouseINRAECNRS31326 Castanet-TolosanFrance

Receptor-like kinases(RLKs)are plasma membrane(PM)proteins that monitor the extracellular environment and regulate various processes such as biotic *** motif(LysM)RLKs are a specific class of RLKs involved in the recognition of chitin-derived molecules produced by microorganisms(Buendia et al.,2018).Notably,the LysM-RLK heterocomplex LjNFR1/LjNFR5 recognizes lipochitooligosaccharides(LCOs,also called Nod factors)leading to root nodule symbiosis(RNS)in Lotus japonicus,whereas the heterocomplexes AtLYK5/AtCERK1 and OsCEBIP/OsCERK1 recognize chitooligosaccharides(COs)leading to defense responses in Arabidopsis thaliana and rice,respectively(Buendia et al.,2018).These receptors function as *** ligand binding activates the intracellular kinase activity of LjNFR1,AtCERK1,and OsCERK1,which mediate phosphorylation-dependent signaling *** mechanisms are essential to tightly control RLK homeostasis and signaling,allowing cells to respond efficiently while preventing constitutive *** PM-resident pool of RLKs must be maintained for rapid response,while RLK endocytosis and ultimately degradation in lytic vacuoles is critical for both signaling and downregulation of the *** addition to its role in proteasome-dependent degradation,ubiquitination,a post-translational protein modification,has emerged as a key regulator of PM proteins by inducing their internalization and degradation in lytic vacuoles(Romero-Barrios and Vert,2018).

关键词： extracellular immunity kinases

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

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

The role of Src family kinases in mediating M-CSF receptor signaling and monocytic cell survival

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Advances in Bioscience and Biotechnology 2012年第5期3卷 592-602页

作者： Yijie Wang Melissa G. Piper Clay B. Marsh Department of Internal Medicine Division of Pulmonary Allergy Critical Care and Sleep Medicine the Dorothy M. Davis Heart and Lung Research Institute Ohio State University Columbus Ohio USA

Previously, we reported that M-CSF induced monocyte survival through the activation of Akt, p38MAPK and Erk1/2 kinases. Here, we found that Src family kinases were upstream of these kinases and played a central role in regulating M-CSF-induced monocyte survival. We observed that M-CSF promoted c-Src activation in monocytes and MDMs in a time-dependent manner. Src inhibitors reduced M-CSF-mediated phosphorylation of the M-CSF receptor (M-CSFR), Akt, Erk1/2, and p38 MAPK. We also observed that Src directly phosphorylated the M-CSFR. Notably, the inhibitors blocked phosphorylation of specific tyrosine residues within the M-CSFR. We further demonstrated that the Src inhibitor, PP2, attenuated M-CSF-induced NF-κB activation and M-CSF-induced monocyte survival. These findings indicated that Src family kinases mediate monocyte survival through the regulation of receptor phosphorylation and modulation of downstream signaling events. Thus, we predict that targeting Src family kinases may have therapeutic implication in inflammatory diseases.

关键词： Monocyte/Macrophage M-CSF Receptor Src Family kinases Cell Survival

Aurora kinases: novel anti-breast cancer targets

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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