Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2006-5-4
pubmed:abstractText
The chemokine receptor CXCR3 is predominantly expressed on activated T and natural killer (NK) cells. CXCR3 and its ligands, CXCL11, CXCL10, and CXCL9, play a major role in T-helper 1 (Th1)-dependent inflammatory responses. CXCL11 is the most dominant physiological inducer of adhesion, migration, and internalization of CXCR3. To study the role of CXCR3 carboxyl-terminus and the third intracellular (3i) loop in chemokine-mediated migration, adhesion, and CXCR3 internalization, we generated CXCR3 receptors mutated in their distal (Ser-Thr domain) or proximal (trileucine domain) membrane carboxyl terminus, and/or the third intracellular loop. We found that migration of CXCR3-expressing HEK 293 cells toward CXCL11 was pertussis toxin-dependent and required the membrane proximal carboxyl terminus of CXCR3. Internalization induced by CXCL11 and protein kinase C (PKC) activation was also regulated by the membrane proximal carboxyl terminus; however, only CXCL11-induced internalization required the LLL motif of this region. Internalization and Ca(2+) flux induced by CXCL11 were independent of the 3i loop S245, whereas migration at high CXCL11 concentrations, integrin-dependent adhesion, and actin polymerization were S245 dependent. Our findings indicate that CXCL11-dependent CXCR3 internalization and cell migration are regulated by the CXCR3 membrane proximal carboxyl terminus, whereas adhesion is regulated by the 3i loop S245. Thus, distinct conformational changes induced by a given CXCR3 ligand trigger different downstream effectors of adhesion, motility, and CXCR3 desensitization.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
107
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3821-31
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:16368892-Amino Acid Sequence, pubmed-meshheading:16368892-Amino Acid Substitution, pubmed-meshheading:16368892-Biological Transport, pubmed-meshheading:16368892-Calcium, pubmed-meshheading:16368892-Calcium Signaling, pubmed-meshheading:16368892-Cell Adhesion, pubmed-meshheading:16368892-Cell Line, pubmed-meshheading:16368892-Cell Movement, pubmed-meshheading:16368892-Chemokine CXCL11, pubmed-meshheading:16368892-Chemokines, CXC, pubmed-meshheading:16368892-DNA Primers, pubmed-meshheading:16368892-Fibronectins, pubmed-meshheading:16368892-Gene Transfer Techniques, pubmed-meshheading:16368892-Humans, pubmed-meshheading:16368892-Kidney, pubmed-meshheading:16368892-Molecular Sequence Data, pubmed-meshheading:16368892-Mutagenesis, Site-Directed, pubmed-meshheading:16368892-Plasmids, pubmed-meshheading:16368892-Receptors, CXCR3, pubmed-meshheading:16368892-Receptors, Chemokine, pubmed-meshheading:16368892-Recombinant Proteins, pubmed-meshheading:16368892-Transfection, pubmed-meshheading:16368892-Vascular Cell Adhesion Molecule-1
pubmed:year
2006
pubmed:articleTitle
Role of CXCR3 carboxyl terminus and third intracellular loop in receptor-mediated migration, adhesion and internalization in response to CXCL11.
pubmed:affiliation
Gene Therapy Institute, Hadassah University Hospital, PO Box 12000, Jerusalem, Israel.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't