tailieunhanh - Báo cáo khoa học: PCSK9 is phosphorylated by a Golgi casein kinase-like kinase ex vivo and circulates as a phosphoprotein in humans

Proprotein convertase subtilisin⁄kexin 9 (PCSK9) is a secreted glycoprotein that regulates the degradation of the low-density lipoprotein receptor. Sin-gle nucleotide polymorphisms in its gene associate with both hypercholes-terolemia and hypocholesterolemia, and studies have shown a significant reduction in the risk of coronary heart disease for ‘loss-of-function’ PCSK9 carriers. | ễFEBS Journal PCSK9 is phosphorylated by a Golgi casein kinase-like kinase ex vivo and circulates as a phosphoprotein in humans Thilina Dewpura1 z Angela Raymond1 z Josee Hamelin2 Nabil G. Seidah2 Majambu Mbikay1 Michel Chretien1 and Janice Mayne1 1 Chronic Disease Program Ottawa Health Research Institute The Ottawa Hospital Canada 2 Laboratory of BiochemicalNeuroendocrinology ClinicalResearch Institute of Montreal Canada Keywords cholesterol hypercholesterolemia kinase PCSK9 phosphoprotein Correspondence J. Mayne Chronic Disease Program Ottawa Health Research Institute 725 Parkdale Avenue Ottawa Ontario K1Y 4E9 Canada Fax 1 613 761 4355 Tel 1 613 798 5555 ext. 16084 E-mail jmayne@ These authors contributed equally to this article Received 4 March 2008 revised 23 April 2008 accepted 6 May 2008 doi Proprotein convertase subtilisin kexin 9 PCSK9 is a secreted glycoprotein that regulates the degradation of the low-density lipoprotein receptor. Single nucleotide polymorphisms in its gene associate with both hypercholesterolemia and hypocholesterolemia and studies have shown a significant reduction in the risk of coronary heart disease for loss-of-function PCSK9 carriers. Previously we reported that proPCSK9 undergoes autocatalytic processing of its prodomain in the endoplasmic reticulum and that its inhibitory prosegment remains associated with it following secretion. Herein we used a combination of mass spectrometry and radiolabeling to report that PCSK9 is phosphorylated at two sites Ser47 in its propeptide and Ser688 in its C-terminal domain. Site-directed mutagenesis suggested that a Golgi casein kinase-like kinase is responsible for PCSK9 phosphorylation based on the consensus site SXE S p . PCSK9 phosphorylation was cell-type specific and occurs physiologically because human plasma PCSK9 is phosphorylated. Interestingly we show that the naturally occurring loss-of-function variant PCSK9 R46L exhibits significantly decreased

• Báo cáo khoa học
• Report medicine
• traditional medicine
• scientific reports
• medical knowledge
• medical research
• analysis of cytoplasmic
• BMC Plant Biology
• Upland cotton
• Restorer gene
• High throughput sequencing
• Cytoplasmic male sterility
• Plant Biology
• Multi omics analysis
• Brassica napus
• Naturally exists
• Mitochondrial genome functions
• BMC Genomics
• RNA sequencing
• Restorer of fertility
• Sterile phenotype
• Parental genes
• Binding miRNAs
• Triple hybrids
• Gossypium bickii
• Proteomic analysis
• biochemistry
• molecular Biology
• microRNA genes
• hemoglobin
• medical analysis
• environmental medicine
• human disease
• Crystal structure
• biochemical studies
• Gossypium hirsutum L
• Photosensitive genetic male sterile
• Differentially expressed genes
• Transcriptome analysis
• RNA Seq
• mammals
• tài liệu báo cáo nghiên cứu khoa học
• cách trình bày báo cáo
• kiến thức bệnh thú y
• báo cáo bệnh thú y
• các nghiên về bệnh thú ý
• scientific research
• Human telomeric
• Structural features
• hormone medicine
• under construction
• cytoplasm
• molecular
• biosynthesis
• genetics
• PPR protein
• Targeted mutagenesis
• Nuclear restorer gene
• Structure function relationship
• Rubber tree
• Hevea brasiliensis
• Genome sequencing
• Anther transcriptome
• Hybrid wheat
• Pistil like
• Skeletal muscle
• Wnt signaling pathway
• Enzyme activity
• Cytoplasmic surface
• Fertility restorer
• Plant breeders
• Nuclear genes