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DOI10.1073/pnas.2002162118
Ras inhibitor CAPRI enables neutrophil-like cells to chemotax through a higher-concentration range of gradients
Xu X.; Wen X.; Moosa A.; Bhimani S.; Jin T.
发表日期2021
ISSN0027-8424
卷号118期号:43
英文摘要Neutrophils sense and migrate through an enormous range of chemoattractant gradients through adaptation. Here, we reveal that in human neutrophils, calcium-promoted Ras inactivator (CAPRI) locally controls the GPCR-stimulated Ras adaptation. Human neutrophils lacking CAPRI (caprikd) exhibit chemoattractant-induced, nonadaptive Ras activation; significantly increased phosphorylation of AKT, GSK-3α/3β, and cofilin; and excessive actin polymerization. caprikd cells display defective chemotaxis in response to high-concentration gradients but exhibit improved chemotaxis in low- or subsensitive-concentration gradients of various chemoattractants, as a result of their enhanced sensitivity. Taken together, our data reveal that CAPRI controls GPCR activation-mediated Ras adaptation and lowers the sensitivity of human neutrophils so that they are able to chemotax through a higher-concentration range of chemoattractant gradients. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Adaptation; CAPRI; Chemotaxis; GAP; Small GTPase Ras
语种英语
scopus关键词calcium promoted Ras inactivator; cofilin; G protein coupled receptor; glycogen synthase kinase 3alpha; glycogen synthase kinase 3beta; guanosine triphosphatase activating protein; protein kinase B; unclassified drug; actin polymerization; adaptation; Article; controlled study; human; human cell; neutrophil chemotaxis; protein function; protein phosphorylation; signal transduction
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/238769
作者单位Chemotaxis Signaling Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD 20852, United States
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Xu X.,Wen X.,Moosa A.,et al. Ras inhibitor CAPRI enables neutrophil-like cells to chemotax through a higher-concentration range of gradients[J],2021,118(43).
APA Xu X.,Wen X.,Moosa A.,Bhimani S.,&Jin T..(2021).Ras inhibitor CAPRI enables neutrophil-like cells to chemotax through a higher-concentration range of gradients.Proceedings of the National Academy of Sciences of the United States of America,118(43).
MLA Xu X.,et al."Ras inhibitor CAPRI enables neutrophil-like cells to chemotax through a higher-concentration range of gradients".Proceedings of the National Academy of Sciences of the United States of America 118.43(2021).
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