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.