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Defective lymphocyte chemotaxis in beta-arrestin2- and GRK6-deficient mice.

dc.contributor.author Fong, AM
dc.contributor.author Lefkowitz, Robert J
dc.contributor.author Patel, DD
dc.contributor.author Premont, Richard Thomas
dc.contributor.author Richardson, RM
dc.contributor.author Yu, Y-RA
dc.coverage.spatial United States
dc.date.accessioned 2013-09-05T15:42:45Z
dc.date.issued 2002-05-28
dc.identifier https://www.ncbi.nlm.nih.gov/pubmed/12032308
dc.identifier.issn 0027-8424
dc.identifier.uri https://hdl.handle.net/10161/7804
dc.description.abstract Lymphocyte chemotaxis is a complex process by which cells move within tissues and across barriers such as vascular endothelium and is usually stimulated by chemokines such as stromal cell-derived factor-1 (CXCL12) acting via G protein-coupled receptors. Because members of this receptor family are regulated ("desensitized") by G protein-coupled receptor kinase (GRK)-mediated receptor phosphorylation and beta-arrestin binding, we examined signaling and chemotactic responses in splenocytes derived from knockout mice deficient in various beta-arrestins and GRKs, with the expectation that these responses might be enhanced. Knockouts of beta-arrestin2, GRK5, and GRK6 were examined because all three proteins are expressed at high levels in purified mouse CD3+ T and B220+ B splenocytes. CXCL12 stimulation of membrane GTPase activity was unaffected in splenocytes derived from GRK5-deficient mice but was increased in splenocytes from the beta-arrestin2- and GRK6-deficient animals. Surprisingly, however, both T and B cells from beta-arrestin2-deficient animals and T cells from GRK6-deficient animals were strikingly impaired in their ability to respond to CXCL12 both in transwell migration assays and in transendothelial migration assays. Chemotactic responses of lymphocytes from GRK5-deficient mice were unaffected. Thus, these results indicate that beta-arrestin2 and GRK6 actually play positive regulatory roles in mediating the chemotactic responses of T and B lymphocytes to CXCL12.
dc.language eng
dc.relation.ispartof Proc Natl Acad Sci U S A
dc.relation.isversionof 10.1073/pnas.112198299
dc.subject Animals
dc.subject Arrestins
dc.subject Chemotaxis, Leukocyte
dc.subject Crosses, Genetic
dc.subject G-Protein-Coupled Receptor Kinase 5
dc.subject G-Protein-Coupled Receptor Kinases
dc.subject GTP-Binding Proteins
dc.subject Gene Expression Regulation
dc.subject Kinetics
dc.subject Lymphocyte Subsets
dc.subject Lymphocytes
dc.subject Mice
dc.subject Mice, Inbred C57BL
dc.subject Mice, Knockout
dc.subject Protein-Serine-Threonine Kinases
dc.subject beta-Arrestins
dc.title Defective lymphocyte chemotaxis in beta-arrestin2- and GRK6-deficient mice.
dc.type Journal article
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/12032308
pubs.begin-page 7478
pubs.end-page 7483
pubs.issue 11
pubs.organisational-group Basic Science Departments
pubs.organisational-group Biochemistry
pubs.organisational-group Chemistry
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Duke Institute for Brain Sciences
pubs.organisational-group Institutes and Centers
pubs.organisational-group Institutes and Provost's Academic Units
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Cardiology
pubs.organisational-group Medicine, Gastroenterology
pubs.organisational-group Medicine, Pulmonary, Allergy, and Critical Care Medicine
pubs.organisational-group Medicine, Rheumatology and Immunology
pubs.organisational-group Pathology
pubs.organisational-group School of Medicine
pubs.organisational-group Trinity College of Arts & Sciences
pubs.organisational-group University Institutes and Centers
pubs.publication-status Published
pubs.volume 99


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