Stromal cell-derived factor 1
- OMIM: 600 835
- UniProt: P48061
- MGI: 103556
CXCL12 (short for CXC motif chemokine 12, and stromal cell-derived factor 1 ( SDF -1) or pre-B cell growth - stimulating factor ( PBSF ) ) is an endogenous neurotransmitter from the group of CXC motif chemokines. As chemotactic acting, that is, the cell movement controlling, cytokine this peptide plays a key role in the mobilization and targeted migration of stem cells in their memory (eg, fetal liver, bone marrow) or their places of use in the formation of organs ( organogenesis ) and of organ and wound healing. CXCL12 is also involved in the growth and metastatic spread of tumors, as well as inflammatory processes. Its effects mediated by this chemokine by binding to two different chemokine receptors, CXCR4 and CXCR7.
- 3.1 Stem cell mobilization
- 3.2 inflammation
- 3.3 cancer
- 3.4 HIV
Occurrence
CXCL12 is produced in high concentrations in the bone marrow and serves the recruitment and anchoring of hematopoietic stem cells. Moreover, CXCL12 is released from other organs in particular of the lungs, the spleen and the liver. Enhanced expression of CXCL12 can be detected in various tumor types.
Biochemistry
Structure
CXCL12 is a protein having a molecular weight of about 8 kDa, encoded by a gene on chromosome 10 q11 locus. The amino acid sequence of this basic protein is largely conserved among mammals, which shows the 99 % homology between the human and mouse CXCL12. There are several, formed by alternative splicing isoforms of CXCL12 known, in particular SDF- 1α and SDF- 1β are of physiological importance. CXC chemokines, such as all is characterized by two cysteine pairs CXCL12, the respective first N-terminal cysteines are separated by one amino acid.
Receptor activation
CXCL12 mediates its effects via binding and activation of the expressed at the cell surface chemokine receptors CXCR4 or CXCR7. These receptors belong to the family of G-protein - coupled receptors. The binding and activation of CXCL12 to CXCR4 is assumed to be two-step process. In a first step CXCL12 binds to the extracellular N-terminus of the receptor. Then, the N -terminal end of the chemokine in the binding pocket of CXCR4, which lies within the transmembrane domains of the receptor, dive in and activate it. In contrast, the activation of CXCR7 is considered less well studied.
Function
Stem cell mobilization
The main function of CXCL12 is to control the migration of stem cells that express the CXCL12 receptor CXCR4. Associated with this CXCL12 plays a crucial role in the attachment of stem cells to their locations and organogenesis. Knockout mice lacking CXCL12 or its receptor CXCR4, are not viable due to severe organ damage. After birth CXCL12 plays an important role in angiogenesis, wound healing and in the repair of organs.
Inflammation
Increased synthesis of CXCL12 in inflamed tissues and chemotactic effect on CXCR4 expressing lymphocytes is contacted with a role in inflammatory diseases in combination.
Cancer
Since the vast majority of tumors express the CXCL12 receptors CXCR4 or CXCR7, CXCL12 shows a chemotactic effect on most tumor cells. This chemotactic effect is one of the main causes for the formation of metastases, which relate in particular to places with high CXCL12 production rate, especially bone marrow, lung and liver. In addition, a CXCL12 support promotion of angiogenesis, tumor growth.
HIV
In addition to the chemotactic effects of CXCL12 on stem cells, tumor cells and inflammatory cells could be detected in HIV -virus inhibitory activity of CXCL12. This is a CXCL12 -induced internalization of the receptor CXCR4 is a co - receptor for the reception of HIV-1 into the host cell, is returned.