SREC-II, a New Member of the Scavenger Receptor Type F Family, Trans-interacts with SREC-I through Its Extracellular Domain

Abstract

The scavenger receptor expressed by endothelial cells (SREC) with an extremely large cytoplasmic domain, was originally identified in a human endothelial cell line. In this study, we have cloned a second isoform named SREC-II and shown that there is a heterophilic interaction between SREC-I and -II at their extracellular domains. The cDNA for murine SREC-II encodes an 834-amino acid protein with 35% homology to SREC-I. Similar to SREC-I, SREC-II contains multiple epidermal growth factor-like repeats in its extracellular domain. However, in contrast to SREC-I, SREC-II had little activity to internalize modified low density lipoproteins (LDL). A Northern blot analysis revealed a tissue expression pattern of SREC-II similar to that of SREC-I with predominant expression in human heart, lung, ovary, and placenta. Mouse fibroblast L cells with no tendency to associate showed noticeable aggregation when SREC-I was overexpressed in these cells, whereas overexpression of SREC-II caused only slight aggregation. Remarkably, intense aggregation was observed when SREC-I-expressing cells were mixed with those expressing SREC-II. Deletion of almost all of the cytoplasmic receptor domain had no effect on the receptor expression and cell aggregation, indicating that solely the extracellular domain is involved in cell aggregation. The association of SREC-I and -II was effectively suppressed by the presence of scavenger receptor ligands such as acetylated LDL and oxidized LDL. These findings suggest that SREC-I and -II show weak cell-cell interaction by their extracellular domains (termed homophilic trans-interaction) but display strong heterophilic transinteraction through the extracellular epidermal growth factor-like repeat domains.

Clever‐1/Stabilin‐1 regulates lymphocyte migration within lymphatics and leukocyte entrance to sites of inflammation

“…The exact function of these domains is still unclear, but they have been reported, e.g. to mediate homophilic and heterophilic protein-protein interactions [19,20]. Recently, a similar domain in a homologous molecule Stabilin-2 has been shown to play a key role in the clearance of aged and apoptotic cells through recognition of the exposed phosphatidyl serine (PS) on the cell surface [21].…”

FEEL-1 and FEEL-2 Are Endocytic Receptors for Advanced Glycation End Products

“…Furthermore, anti-FEEL-1 antibody inhibited the in vitro vascular tube formation (18). On the other hand, SREC-I and its isoform, SREC-II, showed a strong heterophilic trans-interaction through their extracellular EGF-like repeat domains (23).…”

Scavenger Receptor Expressed by Endothelial Cells I (SREC-I) Mediates the Uptake of Acetylated Low Density Lipoproteins by Macrophages Stimulated with Lipopolysaccharide

“…SREC-II encodes an 834-amino acid protein with 35% homology to SREC-I. Although SREC-II has little activity to internalize modified LDL, SREC-I-expressing fibroblasts are intensely aggregated with SREC-II-expressing fibroblasts, indicating the association of SREC-I and SREC-II (7). However, the precise functions of these two proteins are currently unknown.…”

“…Recently, we identified scavenger receptor expressed by endothelial cells I (SREC-I), which encodes a protein of 830 amino acids and binds fluorescent DiI-labeled Ac-LDL when expressed in Chinese hamster ovary cells (6), and its paralogous gene, SREC-II (7). The SREC-I protein is composed of an Nterminal extracellular ligand binding domain with seven epidermal growth factor receptor-like cysteine pattern signatures, a membrane-spanning domain, and an unusually long C-terminal cytoplasmic domain that includes a Ser/Pro-rich region followed by a Gly-rich region.…”