The chemoattractant receptor-like protein C5L2 binds the C3a des-Arg77/acylation-stimulating protein.
The orphan receptor C5L2 has recently been described as a high affinity binding protein for complement fragments C5a and C3a that, unlike the previously described C5a receptor (CD88), couples only weakly to G(i)-like G proteins (Cain, S. A., and Monk, P. N. (2002) J. Biol. Chem. 277, 7165-7169). Here we demonstrate that C5L2 binds the metabolites of C4a and C3a, C4a des-Arg(77), and C3a des-Arg(77) (also known as the acylation-stimulating protein or ASP) at a site distinct from the C5a binding site. The binding of these metabolites to C5L2 does not stimulate the degranulation of transfected rat basophilic leukemia cells either through endogenous rat G proteins or when co-transfected with human G(alpha 16). C3a des-Arg(77)/ASP and C3a can potently stimulate triglyceride synthesis in human skin fibroblasts and 3T3-L1 preadipocytes. Here we show that both cell types and human adipose tissue express C5L2 mRNA and that the human fibroblasts express C5L2 protein at the cell surface. This is the first demonstration of the expression of C5L2 in cells that bind and respond to C3a des-Arg(77)/ASP and C3a. Thus C5L2, a promiscuous complement fragment-binding protein with a high affinity site that binds C3a des-Arg(77)/ASP, may mediate the acylation-stimulating properties of this peptide.
Kalant
David
D
Mike Rosenbloom Laboratory for Cardiovascular Research, Division of Medicine, McGill University Health Centre, Montreal, Quebec H3A 1A1, Canada.
Cain
Stuart A
SA
Maslowska
Magdalena
M
Sniderman
Allan D
AD
Cianflone
Katherine
K
Monk
Peter N
PN
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001798:Blood Proteins / Q000378:metabolism* / Q000502:physiology; D015550:Cell Degranulation / Q000502:physiology; D002460:Cell Line; D015926:Complement C3a / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000502:physiology; D017931:DNA Primers; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D051381:Rats; D044087:Receptor, Anaphylatoxin C5a; D019707:Receptors, Chemokine / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001798:Blood Proteins; C417003:C5aR2 protein, human; D017931:DNA Primers; D044087:Receptor, Anaphylatoxin C5a; D019707:Receptors, Chemokine; C044541:complement C3a, des-Arg-(77)-; D015926:Complement C3a