FRAKTALKINE

A new class of membrane-bound chemokine with a CX₃C motif
J. Fernando Bazan^*, Kevin B. Bacon^†, Gary Hardiman^*, Wei Wang^†, Ken Soo^†, Devora Rossi^†, David R. Greaves^‡, Albert Zlotnik^† & Thomas J. Schall^†
Departments of^* Molecular Biology and ^† Immunology, DNAX Research Institute, 901 California Avenue, Palo Alto, California 94304, USA
^‡ Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK 




Chemokines direct the trafficking of white blood cells in immune surveillance, playing a key role in inflammatory and infectious diseases such as AIDS^1–5. 

All chemokines studied so far are secreted proteins of relative molecular mass 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-aminoacid 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.