SDF-1β binds primarily to CXCR4, a G-protein-coupled receptor critical for:
Stem Cell Homing: Directs hematopoietic stem cells to bone marrow niches .
Cancer Metastasis: Facilitates tumor cell migration to SDF-1-rich microenvironments (e.g., bone marrow in multiple myeloma) .
Angiogenesis: Promotes endothelial cell proliferation via VEGF synergy .
Secondary interactions with CXCR7 modulate cell adhesion and survival pathways .
Key pathways activated by SDF-1β include:
FAK/PI3K/Akt: Mediates cytoskeletal reorganization during cell migration .
GSK3β/β-Catenin: Enhances transcriptional activation of pro-survival genes .
Tumor Microenvironment: SDF-1β secreted by bone marrow stromal cells enhances multiple myeloma cell adhesion and growth (in vivo murine models) .
Therapeutic Targeting: Neutralizing SDF-1β in bone marrow niches reduces tumor cell colonization by 60–80% .
Stem Cell Recruitment: SDF-1β gradients guide dental pulp stem cells (hDPSCs) to injury sites via CXCR4 activation, enabling tissue repair .
Cardioprotection: Upregulated SDF-1β in ischemic heart tissue recruits progenitor cells, improving post-infarction recovery .
HIV Pathogenesis: CXCR4 serves as a co-receptor for HIV-1 entry, making SDF-1β a potential inhibitor via receptor blockade .
Isoform | Length (a.a.) | Stability | Primary Tissue Localization | Key Function |
---|---|---|---|---|
SDF-1α | 68 | Labile in serum | Ubiquitous | Leukocyte chemotaxis |
SDF-1β | 93 | Serum-resistant | Liver, spleen, kidneys | Angiogenesis, stem cell retention |
SDF-1γ | 119 | Not well characterized | Heart, brain | Ischemia response |
Recombinant SDF-1β is purified using proprietary chromatographic techniques, yielding >95% purity (SDS-PAGE verified) . Lyophilized formulations retain activity for >12 months at -20°C . Functional assays confirm binding to CXCR4 with a linear range of 0.02–2.5 µg/mL .
MGSSHHHHHH SSGLVPRGSH MKPVSLSYRC PCRFFESHVA RANVKHLKIL NTPNCALQIV ARLKNNNRQV CIDPKLKWIQ EYLEKALNKR FKM.
Stromal Cell-Derived Factor-1 (SDF-1), also known as C-X-C motif chemokine 12 (CXCL12), is a chemokine protein encoded by the CXCL12 gene in humans . This protein plays a crucial role in various physiological processes, including embryogenesis, immune surveillance, inflammation response, tissue homeostasis, and tumor growth and metastasis .
The CXCL12 gene is located on chromosome 10 at the band 10q11.21 and contains four exons . This gene produces seven isoforms through alternative splicing, with SDF-1α (CXCL12a) and SDF-1β (CXCL12b) being the most studied . The protein belongs to the intercrine alpha (chemokine CXC) family and is characterized by the presence of four conserved cysteines that form two disulfide bonds .
CXCL12 is ubiquitously expressed in many tissues and cell types, including the brain, thymus, heart, lung, liver, kidney, spleen, platelets, and bone marrow . It is a potent chemoattractant for lymphocytes and plays a significant role in directing the migration of hematopoietic cells from the fetal liver to the bone marrow during embryogenesis . CXCL12 activates the C-X-C chemokine receptor CXCR4, inducing a rapid and transient rise in intracellular calcium ions and chemotaxis .
Recombinant CXCL12, particularly the human recombinant form with a His tag, is used in various research applications. The His tag facilitates the purification of the protein using affinity chromatography, making it easier to study its structure and function in detail.