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Role and mechanism of action of leucine-rich repeat kinase 1 in bone 被引量:2
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作者 Weirong Xing Helen Goodluck +1 位作者 Canjun Zeng Subburaman Mohan 《Bone Research》 SCIE CAS CSCD 2017年第1期14-26,共13页
Leucine-rich repeat kinase 1 (LRRK1) plays a critical role in regulating cytoskeletal organization, osteoclast activity, and bone resorption with little effect on bone formation parameters. Deficiency of Lrrkl in mi... Leucine-rich repeat kinase 1 (LRRK1) plays a critical role in regulating cytoskeletal organization, osteoclast activity, and bone resorption with little effect on bone formation parameters. Deficiency of Lrrkl in mice causes a severe osteopetrosis in the metaphysis of the long bones and vertebrae bones, which makes LRRK1 an attractive alternative drug target for the treatment of osteoporosis and other high-turnover bone diseases. This review recent advances on the functions of the Lrrkl-related family members, Lrrkl deficiency-induced skeletal phenotypes, LRRK1 structure-function, potential biological substrates and interacting proteins, and the mechanisms of LRRK1 action in osteoclasts. 展开更多
关键词 GENE Role and mechanism of action of leucine-rich repeat kinase 1 in bone
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Evolutionary dynamics of leucine‐rich repeat receptor‐like kinases and related genes in plants:A phylogenomic approach 被引量:2
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作者 Tao Shi Hongwen Huang +1 位作者 Michael J.Sanderson Frans E.Tax 《Journal of Integrative Plant Biology》 SCIE CAS CSCD 2014年第7期648-662,共15页
Leucine-rich repeat (LRR) receptor-like kinases (RLKs), evolutionarily related LRR receptor-like proteins (RLPs) and receptor-like cytoplasmic kinases (RLCKs) have important roles in plant signaling, and their... Leucine-rich repeat (LRR) receptor-like kinases (RLKs), evolutionarily related LRR receptor-like proteins (RLPs) and receptor-like cytoplasmic kinases (RLCKs) have important roles in plant signaling, and their gene subfamilies are large with a complicated history of gene duplication and loss. In three pairs of closely related lineages, including Arabidopsis thaliana and A. lyrata (Arabidopsis), Lotus japonicus, and Medicago truncatula (Legumes), Oryza sativa ssp. japonica, and O. sativa ssp. indica (Rice), we find that LRR RLKs comprise the largest group of these LRR-related subfamilies, while the related RLCKs represent the smal est group. In addition, comparison of orthologs indicates a high frequency of reciprocal gene loss of the LRR RLK/LRR RLP/RLCK subfamilies. Furthermore, pairwise comparisons show that reciprocal gene loss is often associated with lineage-specific duplication(s) in the alternative lineage. Last, analysis of genes in A. thaliana involved in development revealed that most are highly conserved orthologs without species-specific duplication in the two Arabidopsis species and originated from older Arabidopsis-specific or rosid-specific duplications. We discuss&amp;nbsp;potential pitfal s related to functional prediction for genes that have undergone frequent turnover (duplications, losses, and domain architecture changes), and conclude that prediction based on phylogenetic relationships wil likely outperform that based on sequence similarity alone. 展开更多
关键词 Domain architecture evolution gene duplication and loss leucine-rich repeat receptor-like kinases leucine-rich repeat receptor-like proteins receptor-like cytoplasmic kinases
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Axonal growth inhibitors and their receptors in spinal cord injury:from biology to clinical translation 被引量:2
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作者 Sílvia Sousa Chambel Célia Duarte Cruz 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第12期2573-2581,共9页
Axonal growth inhibitors are released during traumatic injuries to the adult mammalian central nervous system, including after spinal cord injury. These molecules accumulate at the injury site and form a highly inhibi... Axonal growth inhibitors are released during traumatic injuries to the adult mammalian central nervous system, including after spinal cord injury. These molecules accumulate at the injury site and form a highly inhibitory environment for axonal regeneration. Among these inhibitory molecules, myelinassociated inhibitors, including neurite outgrowth inhibitor A, oligodendrocyte myelin glycoprotein, myelin-associated glycoprotein, chondroitin sulfate proteoglycans and repulsive guidance molecule A are of particular importance. Due to their inhibitory nature, they represent exciting molecular targets to study axonal inhibition and regeneration after central injuries. These molecules are mainly produced by neurons, oligodendrocytes, and astrocytes within the scar and in its immediate vicinity. They exert their effects by binding to specific receptors, localized in the membranes of neurons. Receptors for these inhibitory cues include Nogo receptor 1, leucine-rich repeat, and Ig domain containing 1 and p75 neurotrophin receptor/tumor necrosis factor receptor superfamily member 19(that form a receptor complex that binds all myelin-associated inhibitors), and also paired immunoglobulin-like receptor B. Chondroitin sulfate proteoglycans and repulsive guidance molecule A bind to Nogo receptor 1, Nogo receptor 3, receptor protein tyrosine phosphatase σ and leucocyte common antigen related phosphatase, and neogenin, respectively. Once activated, these receptors initiate downstream signaling pathways, the most common amongst them being the Rho A/ROCK signaling pathway. These signaling cascades result in actin depolymerization, neurite outgrowth inhibition, and failure to regenerate after spinal cord injury. Currently, there are no approved pharmacological treatments to overcome spinal cord injuries other than physical rehabilitation and management of the array of symptoms brought on by spinal cord injuries. However, several novel therapies aiming to modulate these inhibitory proteins and/or their receptors are under investigation in ongoing clinical trials. Investigation has also been demonstrating that combinatorial therapies of growth inhibitors with other therapies, such as growth factors or stem-cell therapies, produce stronger results and their potential application in the clinics opens new venues in spinal cord injury treatment. 展开更多
关键词 chondroitin sulphate proteoglycans collapsin response mediator protein 2 inhibitory molecules leucine-rich repeat and Ig domain containing 1 leucocyte common antigen related myelin-associated glycoprotein neurite outgrowth inhibitor A Nogo receptor 1 Nogo receptor 3 oligodendrocyte myelin glycoprotein p75 neurotrophin receptor Plexin A2 Ras homolog family member A/Rho-associated protein kinase receptor protein tyrosine phosphataseσ repulsive guidance molecule A spinal cord injury tumour necrosis factor receptor superfamily member 19
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ORYZA SATIVA SPOTTED-LEAF 41(OsSPL41) Negatively Regulates Plant Immunity in Rice
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作者 TAN Jingyi ZHANG Xiaobo +7 位作者 SHANG Huihui LI Panpan WANG Zhonghao LIAO Xinwei XU Xia YANG Shihua GONG Junyi WU Jianli 《Rice science》 SCIE CSCD 2023年第5期426-436,I0017-I0020,共15页
Identification of immunity-associated leucine-rich repeat receptor-like protein kinases(LRR-RLK) is critical to elucidate the LRR-RLK mediated mechanism of plant immunity.Here,we reported the map-based cloning of a no... Identification of immunity-associated leucine-rich repeat receptor-like protein kinases(LRR-RLK) is critical to elucidate the LRR-RLK mediated mechanism of plant immunity.Here,we reported the map-based cloning of a novel rice SPOTTED-LEAF 41(Os SPL41) encoding a putative LRR-RLK protein(Os LRR-RLK41/Os SPL41) that regulated disease responses to the bacterial blight pathogen Xanthomonas oryzae pv.oryzae(Xoo).An 8-bp insertion at position 865 bp in a mutant spotted-leaf 41(spl41) allele led to the formation of purple-brown lesions on leaves.Functional complementation by the wild type allele(Os SPL41) can rescue the mutant phenotype,and the complementary lines showed similar performance to wild type in a number of agronomic,physiological and molecular indices.Os SPL41 was constitutively expressed in all tissues tested,and Os SPL41 contains a typical transmembrane domain critical for its localization to the cell membrane.The mutant exhibited an enhanced level of resistance to Xoo in companion of markedly up-regulated expression of pathogenesis-related genes such as Os PR10a,Os PAL1 and Os NPR1,while the level of salicylic acid was significantly increased in spl41.In contrast,the over-expression lines exhibited a reduced level of H_(2)O_(2) and were much susceptible to Xoo with down-regulated expression of pathogenesis-related genes.These results suggested that Os SPL41 might negatively regulate plant immunity through the salicylic acid signaling pathway in rice. 展开更多
关键词 bacterial blight leucine-rich repeat receptor-like protein kinase plant immunity reactive oxygen species RICE spotted leaf
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Pseudomonas Cyclic Lipopeptide Medpeptin:Biosynthesis and Modulation of Plant Immunity
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作者 Yi-Lin Gu Jun-Zhou Li +4 位作者 Yan Li Shen Cong Jing Wang Yi-Nan Ma Hai-Lei Wei 《Engineering》 SCIE EI CAS CSCD 2023年第9期153-165,共13页
The multifunctional secondary metabolites known as cyclic lipopeptides(CLPs),which are produced by a large variety of bacteria,have become a key category of plant immunity elicitors.Pseudomonas-CLPs(PsCLPs)are extreme... The multifunctional secondary metabolites known as cyclic lipopeptides(CLPs),which are produced by a large variety of bacteria,have become a key category of plant immunity elicitors.Pseudomonas-CLPs(PsCLPs)are extremely diverse in structure and biological activity.However,an understanding of CLP-plant structure–function interactions currently remains elusive.Here,we identify medpeptin,a novel CLP from Pseudomonas mediterranea that consists of 22 amino acids.Medpeptin is synthesized by a non-ribosomal peptide synthase(NRPS)gene cluster and regulated by a quorum-sensing system.Further research indicates that medpeptin does not exhibit antimicrobial activity;instead,it induces plant cell death immunity and confers resistance to bacterial infection.Comparative transcriptome analysis and virus-induced gene silencing(VIGS)reveal a set of immune signaling candidates involved in medpeptin perception.Silencing of a cell-wall leucine-rich repeat extensin protein(NbLRX3)or a receptor-like protein kinase(NbRLK25)—but not BAK1 or SGT1—compromises medpeptin-triggered cell death and resistance to pathogen infection in Nicotiana benthamiana.Our findings point to a noncanonical mechanism of CLP sensing and suggest perspectives for the development of plant disease resistance. 展开更多
关键词 PSEUDOMONAS Cyclic lipopeptide Cell death leucine-rich repeat extension(LRX) Medpeptin receptor-like kinase(RLK)
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Cloning and Preliminary Characterization of Three Receptor-like Kinase Genes in Soybean
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作者 Yuan-Yuan Ma Li-Wen Zhang +5 位作者 Peng-Li Li Rui Gan Xiao-Ping Li Ren Zhang Yong Wang Ning-Ning Wang 《Journal of Integrative Plant Biology》 SCIE CAS CSCD 2006年第11期1338-1347,共10页
Leaf senescence that occurs in the last stage of leaf development is a genetically programmed process. It is very significant to isolate the upstream components in the senescence signaling pathway and to elucidate the... Leaf senescence that occurs in the last stage of leaf development is a genetically programmed process. It is very significant to isolate the upstream components in the senescence signaling pathway and to elucidate the molecular mechanisms that control the initiation and progression of leaf senescence. In this study, full-length cDNAs of three receptor-like protein kinase genes, designated rlpkl, rlpk2 and rlpk3, were cloned from artificially-induced senescent soybean (Glycine max L.) primary leaves (GenBank accession AY687390, AY687391, AF338813). The deduced amino acid sequences indicated that they belonged to a receptor-like kinase family. Each of rlpkl and rlpk2 encodes a leucine-rich repeat (LRR) receptor-like protein kinase. They both comprise a typical signal peptide, several LRR motifs, a single-pass transmembrane domain, and a cytoplasmic protein kinase domain. No typical extracellular domain of RLPK3 was predicted. Organ-specific expression pattern analysis by reverse-transcription polymerase chain reaction (RT-PCR) revealed higher expression levels of the three genes in cotyledons, roots and flowers. Phylogenetic analysis indicated that RLPK1 and RLPK2 belonged to an independent branch, whereas RLPK3 shared common nodes with several known RLKs responding to ablotic and biotic stresses. The evident alternations of expression profiles of rlpkl and rlpk2 induced by the artificial senescence-inducing treatment implied involvements of these two RLKs in regulating soybean leaf senescence. 展开更多
关键词 gene expression Glycine max: leaf senescence leucine-rich repeat phylogenesis analysis receptor-like kinase.
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LRRK2G2019S Mutation Inhibits Degradation of α-Synuclein in an In Vitro Model of Parkinson's Disease 被引量:1
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作者 Dan HU Jian-yi NIU +3 位作者 Jing XIONG Shu-ke NIE Fei ZENG Zhao-hui ZHANG 《Current Medical Science》 SCIE CAS 2018年第6期1012-1017,共6页
The G2019S mutation of the leucine-rich repeat kinase 2(LRRK2)is the most common genetic cause of Parkinson's disease (PD).However,the molecular mechanisms of LRRK2 mutation contributing to the onset and progressi... The G2019S mutation of the leucine-rich repeat kinase 2(LRRK2)is the most common genetic cause of Parkinson's disease (PD).However,the molecular mechanisms of LRRK2 mutation contributing to the onset and progression of PD have not been fully illustrated.We generated HEK293 cells stably transfected with α-synuclein and investigated the effect of LRRK2 G2019S mutation on the degradation of α-synuclein.The lysosomal activity was assessed by the protein degradation of glyceraldehyde-3-phosphate dehydrogenase and ribonuclease A.It was found that α-synuclein was mainly degraded in lysosomes.LRRK2G2019S inhibited the degradation of α-synuclein,and promoted its aggregation.LRRK2G 2019S also decreased the activities of lysosomal enzymes including cathepsin B and cathepsin L.Furthermore,the inhibitory effect of LRRK2 G2019S on lysosomal functions did not depend on its kinase activity.These findings indicated that the inhibitory effect of LRRK2 G2019S on α-synuclein degradation could underlie the pathogenesis of aberrant α-synuclein aggregation in PD with LRRK2 mutation. 展开更多
关键词 Α-SYNUCLEIN leucine-rich repeat kinasE 2 Parkinson's disease LYSOSOME
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Cloning and Sequence Analysis of Disease Resistance Gene Analogues from Three Wild Rice Species in Yunnan 被引量:1
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作者 LIUJ-i-mei YANGMing-zhi 《Agricultural Sciences in China》 CAS CSCD 2003年第3期265-272,共8页
Two sets of degenerate oligonucleotide primers were designed according to amino acid conserved regions of reported plant disease resistance genes which encode proteins that contain nucleotide-binding site and leucine-... Two sets of degenerate oligonucleotide primers were designed according to amino acid conserved regions of reported plant disease resistance genes which encode proteins that contain nucleotide-binding site and leucine-rich repeats(NBS-LRR), and the plant disease resistance genes which encode serine/threonine protein kinase(STK). By polymerase chain reaction(PCR), disease resistance gene analogues have been amplified from three wild rice species in Yunnan Province, China. The DIN A fragments from amplification have been cloned into the pGEM-T vector respectively. Sequencing of the DNA fragments indicated that 7 classes, 2 classes and 6 classes NBS-LRR disease resistance gene analogues from Oryza rufipogon Griff. , Oryza officinalis Wall. , and Oryza meyeriana Baill. were obtained respectively. The two representative fragments of TO12 from Oryza officinalis Wall, and TR19 from Oryza rufipogon Griff, belong to the same class and homology of their sequences are 100%. The result shows that the sequences of the same class disease resistance gene analogues have no difference among different species of wild rice. 5 classes STK disease resistance gene analogues were also obtained among which 4 classes from Oryza rufipogon Griff. , 1 class from Oryza officinalis Wall. By comparison analysis of amino acid sequences. we found that the obtained disease resistance gene analogues have very low identity(low to 25%) with the reported disease resistance gene L6, N, Bs2, Prf, Pto, Lr10 and Xa21 etc. The finding suggests that the obtained disease resistance gene analogues are analogues of putative disease resistance genes that have not been isolated so far. 展开更多
关键词 Wild rice Disease-resistance gene Nucleotide-binding site ( NBS) leucine-rich repeat (LRR) Serine/threonine protein kinase(STK) ANALOGUES
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Crystal structure of a plant leucine rich repeat protein with two island domains 被引量:2
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作者 SONG Wen HAN ZhiFu +1 位作者 SUN YaDong CHAI JiJie 《Science China(Life Sciences)》 SCIE CAS 2014年第1期137-144,共8页
Leucine rich repeat(LRR)domain,characterized by a repetitive sequence pattern rich in leucine residues,is a universal protein-protein interaction motif present in all life forms.LRR repeats interrupted by sequences of... Leucine rich repeat(LRR)domain,characterized by a repetitive sequence pattern rich in leucine residues,is a universal protein-protein interaction motif present in all life forms.LRR repeats interrupted by sequences of 30 70 residues(termed island domain,ID)have been found in some plant LRR receptor-like kinases(RLKs)and animal Toll-like receptors(TLR7-9).Recent studies provide insight into how a single ID is structurally integrated into an LRR protein.However,structural information on an LRR protein with two IDs is lacking.The receptor-like protein kinase 2(RPK2)is an LRR-RLK and has important roles in controlling plant growth and development by perception and transduction of hormone signal.Here we present the crystal structure of the extracellular LRR domain of RPK2(RPK2-LRR)containing two IDs from Arabidopsis.The structure reveals that both of the IDs are helical and located at the central region of the single RPK2-LRR solenoid.One of them binds to the inner surface of the solenoid,whereas the other one mainly interacts with the lateral side.Unexpectedly,a long loop immediately following the N-terminal capping domain of RPK2-LRR is presented toward and sandwiched between the two IDs,further stabilizing their embedding to the LRR solenoid.A potential ligand binding site formed by the two IDs and the solenoid is located at the C-terminal side of RPK2-LRR.The structural information of RPK2-LRR broadens our understanding toward the large family of LRR proteins and provides insight into RPK2-mediated signaling. 展开更多
关键词 leucine rich repeat receptor-like kinases receptor-like protein kinase 2
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Chemical control of receptor kinase signaling by rapamycin-induced dimerization
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作者 Sara Kim Jeonghyang Park +6 位作者 Byeong Wook Jeon Geonhee Hwang Na Young Kang Yeim We Won-Young Park Eunkyoo Oh Jungmook Kim 《Molecular Plant》 SCIE CAS CSCD 2021年第8期1379-1390,共12页
Membrane-localized leucine-rich repeat receptor kinases(LRR-RKs)sense diverse extracellular signals,and coordinate and specify cellular functions in plants.However,functional understanding and identification of the ce... Membrane-localized leucine-rich repeat receptor kinases(LRR-RKs)sense diverse extracellular signals,and coordinate and specify cellular functions in plants.However,functional understanding and identification of the cellular signaling of most LRR-RKs remain a major challenge owing to their genetic redundancy,the lack of ligand information,and subtle phenotypes of LRR-RK overexpression.Here,we report an engineered rapamycin-inducible dimerization(RiD)receptor system that triggers a receptor-specific LRR-RK signaling independent of their cognate ligands or endogenous receptors.Using the RiD-receptors,we demonstrated that the rapamycin-mediated association of chimeric cytosolic kinase domains from the BRI1/BAK1 receptor/co-receptor,but not the BRI1/BRI1 or BAK1/BAK1 homodimer,is sufficient to activate downstream brassinosteroid signaling and physiological responses.Furthermore,we showed that the engineered RiD-FLS2/BAK1 could activate flagellin-22-mediated immune signaling and responses.Using the RiD system,we also identified the potential function of an unkmown orphan receptor in immune signaling and revealed the differential activities of SERK co-receptors of LRR-RKs.Our results indicate that the RiD method can serve as a synthetic biology tool for precise temporal manipulation of LRR-RK signaling and for understanding LRR-RK biology. 展开更多
关键词 leucine-rich repeat receptor kinase BRASSINOSTEROIDS BRI1 BAK1 FLS2
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CLE Peptides in Plants:Proteolytic Processing,Structure-Activity Relationship,and Ligand-Receptor Interaction 被引量:10
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作者 Xiaoming Gao Yongfeng Guo 《Journal of Integrative Plant Biology》 SCIE CAS CSCD 2012年第10期738-745,共8页
Ligand-receptor signaling initiated by the CLAVATA3/ENDOSPERM SURROUNDING REGION (CLE) family peptides is critical in regulating cell division and differentiation in meristematic tissues in plants. Biologically acti... Ligand-receptor signaling initiated by the CLAVATA3/ENDOSPERM SURROUNDING REGION (CLE) family peptides is critical in regulating cell division and differentiation in meristematic tissues in plants. Biologically active CLE peptides are released from precursor proteins via proteolytic processing. The mature form of CLE ligands consists of 12-13 amino acids with several post-translational modifications. This review summarizes recent progress toward understanding the proteolytic activities that cleave precursor proteins to release CLE peptides, the molecular structure and function of mature CLE ligands, and interactions between CLE ligands and cor- responding leucine-rich repeat (LRR) receptor-like kinases (RLKs). 展开更多
关键词 CLV3 leucine-rich repeat receptor-like kinase MERISTEM NODULATION stem cell.
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BAK1 Directly Regulates Brassinosteroid Perception and BRI1 Activation 被引量:12
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作者 Kai He Shengbao Xu Jia Li 《Journal of Integrative Plant Biology》 SCIE CAS CSCD 2013年第12期1264-1270,共7页
Plants utilize plasma membrane-localized receptor-like kinases (RLKs) to sense extracellular signals to coordinate growth, development, and innate immune responses. BAK1 regulates multiple signaling pathways acting ... Plants utilize plasma membrane-localized receptor-like kinases (RLKs) to sense extracellular signals to coordinate growth, development, and innate immune responses. BAK1 regulates multiple signaling pathways acting as a co-receptor of several distinct ligand-binding RLKs. It has been debated whether BAK1 serves as an essential regulatory component or only a signal amplifier without pathway specificity. This issue has been clarified recently. Genetic and structural analyses indicated that BAK1 and its homologs play indispensible roles in mediating brassinosteroid (BR) signaling pathway by directly perceiving the ligand BR and activating the receptor of BR, BRII. The mechanism revealed by these studies now serves as a paradigm for how a pair of RLKs can function together in ligand binding and subsequent initiation of signaling. 展开更多
关键词 ARABIDOPSIS BAK1 BRASSINOSTEROID BRI1 CO-RECEPTOR extracellular domain leucine-rich repeat RECEPTOR receptor-like kinase.
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