Identification and partial characterization of a variant of human CXCR3 generated by posttranscriptional exon skipping.
Chemokines are recognized as functionally important in many pathological disorders, which has led to increased interest in mechanisms related to the regulation of chemokine receptor (CKR) expression. Known mechanisms for regulating CKR activity are changes in gene expression or posttranslational modifications. However, little is known about CKR with respect to a third regulatory mechanism, which is observed among other seven-transmembrane receptor subfamilies, the concept of differential splicing or processing of heteronuclear RNA. We now report on the discovery of a variant human CKR, CXCR3, resulting from alternative splicing via exon skipping. The observed RNA processing entails a drastically altered C-terminal protein sequence with a predicted four- or five-transmembrane domain structure, differing from all known functional CKR. However, our data indicate that that this splice variant, which we termed CXCR3-alt, despite its severe structural changes still localizes to the cell surface and mediates functional activity of CXCL11.
Ehlert
Jan Erik
JE
Proqinase GmbH, Freiburg, Germany.
Addison
Christina A
CA
Burdick
Marie D
MD
Kunkel
Steven L
SL
Strieter
Robert M
RM
D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000502:physiology; D002633:Chemotaxis / Q000235:genetics; D005091:Exons / Q000235:genetics; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
C515202:CXCL11 protein, human; C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine