A new class of membrane-bound chemokine with a CX3C motif.
Chemokines direct the trafficking of white blood cells in immune surveillance, playing a key role in inflammatory and infectious diseases such as AIDS. All chemokines studied so far are secreted proteins of relative molecular mass approximately 7K-15K and fall into three families that are defined by a cysteine signature motif: CXC, CC and C (refs 3, 6, 7), where C is a cysteine and X any amino-acid residue. We report here the identification and characterization of a fourth human chemokine type, derived from non-haemopoietic cells and bearing a new CX3C fingerprint. Unlike other chemokine types, the polypeptide chain of the human CX3C chemokine is predicted to be part of a 373-amino-acid protein that carries the chemokine domain on top of an extended mucin-like stalk. This molecule can exist in two forms: either membrane-anchored or as a shed 95K glycoprotein. The soluble CX3C chemokine has potent chemoattractant activity for T cells and monocytes, and the cell-surface-bound protein, which is induced on activated primary endothelial cells, promotes strong adhesion of those leukocytes. The structure, biochemical features, tissue distribution and chromosomal localization of CX3C chemokine all indicate that it represents a unique class of chemokine that may constitute part of the molecular control of leukocyte traffic at the endothelium.
Bazan
J F
JF
Department of Molecular Biology, DNAX Research Institute, Palo Alto, California 94304, USA.
Bacon
K B
KB
Hardiman
G
G
Wang
W
W
Soo
K
K
Rossi
D
D
Greaves
D R
DR
Zlotnik
A
A
Schall
T J
TJ
D000595:Amino Acid Sequence; D002460:Cell Line; D054428:Chemokine CX3CL1; D018925:Chemokines / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020523:Chemokines, CX3C; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D018076:DNA, Complementary; D006801:Humans; D006822:Hybrid Cells; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D014018:Tissue Distribution
C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D018925:Chemokines; D020523:Chemokines, CX3C; D018076:DNA, Complementary; D008565:Membrane Proteins; D012333:RNA, Messenger