Chemokine Receptors: Overview Philip M. Murphy* Molecular Signaling Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA * corresponding author tel: 301-496-2877, fax: 301-402-4369, e-mail:
[email protected] DOI: 10.1006/rwcy.2000.02012.
INTRODUCTION Chemokine receptors are defined by their ability to bind chemokines in a specific and saturable manner, and to transduce a cellular response. At the molecular level, this definition has been met by 16 human cell surface proteins (named CXCR1 to CXCR5, CCR1 to CCR9, XCR1, and CX3CR1), which together comprise the largest known structurally defined division of the rhodopsin superfamily of seven transmembrane domain, G protein-coupled receptors (GPCRs) (Murphy, 1994; Premack and Schall, 1996; Yoshie et al., 1997; Locati and Murphy, 1999; Zlotnik et al., 1999). In addition, four herpesvirus-encoded chemokine receptors (ORFs US28 of human cytomegalovirus, ECRF3 of herpesvirus saimiri, UL12 of HHV-6 and no. 74 of HHV-8/Kaposi's sarcoma herpesvirus (KSHV; also known as KSHV GPCR) (Isegawa et al., 1998; Pease and Murphy, 1998), and two nonsignaling mammalian chemokine-binding proteins (D6 and the Duffy antigen receptor for chemokines, DARC) (Horuk et al., 1994; Nibbs et al., 1997) have been described. Studied initially for their roles in leukocyte trafficking, chemokine receptors are now known to have multiple additional functions, including regulation of development of the cardiovascular, gastrointestinal, immune, and central nervous systems (Tachibana et al., 1998; Zou et al., 1998), and usage as cell entry factors by HIV-1 (Cocchi et al., 1995; Feng et al., 1996; Berger et al., 1999) and Plasmodium vivax (Horuk et al., 1993), the causative agents of