Recombinant Human CXCL12/SDF-1 gamma Protein

Human CXCL12 is expressed as five isoforms that differ only in the C-terminal tail (1). The gamma isoform of CXCL12, also known as SDF-1 gamma, is a 12 kDa, heparin-binding member of the CXC (or alpha) family of chemokines (2, 3). Mature SDF-1 molecules are not glycosylated and exhibit a typical three antiparallel beta-strand chemokine-like fold. N-terminal aa 1 ‑ 8 form a receptor binding site, while aa 1 and 2 (Lys‑Pro) are involved in receptor activation (4). All SDF-1 isoforms can undergo proteolytic processing of the first two N-terminal amino acids by CD26, which is thought to create a reduced‑activity chemokine (5). Human SDF-1 gamma is synthesized as a 119 amino acid (aa) precursor that contains a 21 aa signal sequence and a 98 aa mature region (1). Mature human SDF-1 gamma shares 99%, 97% and 98% aa identity with mouse, rat, and equine SDF-1 gamma, respectively. The unique C‑terminal 26 aa of SDF-1 gamma are highly charged, including four BBXB (where B = basic and X = any aa) motifs, while the most prevalent form, SDF-1 alpha, has 4 unique C‑terminal aa and binds heparin via the shared BBXB site more N‑terminally located (2, 6). The SDF‑1 gamma C‑terminus binds heparin in secreted SDF-1 gamma, or targets the isoform to the nucleolus in the absence of a signal sequence (6 ‑ 8). SDF-1 isoforms interact with CXCR4 and CXCR7 receptors on the cell surface, and can also bind syndecan-4 (9 ‑ 12). SDF-1 alpha or beta are known to influence lymphopoiesis, enhance the survival of myeloid progenitor cells, regulate the patterning and cell number of neural progenitors, and promote angiogenesis (2). Of all SDF-1 isoforms, SDF-1 gamma is the most strongly attached to the cell surface via glycans, least likely to circulate, and most active in binding CXCR4 and blocking HIV entry to cells via CXCR4 (9, 13). Unlike other isoforms, it is constitutively expressed mainly in the heart or rodent brain, and is not expressed prenatally (14 ‑ 16).