Function: Chemoattractant active on T-lymphocytes, monocytes, but not neutrophils. Activates the C-X-C chemokine receptor CXCR4 to induce a rapid and transient rise in the level of intracellular calcium ions and chemotaxis. Also binds to atypical chemokine receptor ACKR3, which activates the beta-arrestin pathway and acts as a scavenger receptor for SDF-1. Acts as a positive regulator of monocyte migration and a negative regulator of monocyte adhesion via the LYN kinase. Stimulates migration of monocytes and T-lymphocytes through its receptors, CXCR4 and ACKR3, and decreases monocyte adherence to surfaces coated with ICAM-1, a ligand for beta-2 integrins. SDF1A/CXCR4 signaling axis inhibits beta-2 integrin LFA-1 mediated adhesion of monocytes to ICAM-1 through LYN kinase. Plays a protective role after myocardial infarction. Induces down-regulation and internalization of ACKR3 expressed in various cells
By similarity. Has several critical functions during embryonic development; required for B-cell lymphopoiesis, myelopoiesis in bone marrow and heart ventricular septum formation. Ref.3 Ref.9Stimulates the proliferation of bone marrow-derived b progenitor cells in the presence of IL-7 as well as growth of the stromal cell-dependent B-cell clone DW34 cells. Ref.3 Ref.9
Subunit structure: Monomer or homodimer; in equilibrium. Dimer formation is induced by non acidic pH and the presence of multivalent anions, and by binding to CXCR4 or heparin. Monomeric form is required for full chemotactic activity and resistance to ischemia/reperfusion injury, whereas the dimeric form acts as a partial agonist of CXCR4, stimulating Ca2+ mobilization but with no chemotactic activity and instead acts as a selective antagonist that blocks chemotaxis induced by the monomeric form. Interacts with the N-terminus of ACKR3
By similarity.
Subcellular location: Secreted.
Tissue specificity: Highest expression levels detected in kidney, liver, spleen and muscle. Isoform Alpha is expressed ubiquitously but at varying levels, while isoform Beta displays tissue-specific expression, with expression detected in kidney, liver, heart, spleen and muscle but not in lung, colon, brain, skin and stomach. Ref.2
Induction: Down-regulated by 12-O-tetradecanoylphorbol 13-acetate (TPA), with 5-fold decrease in expression levels at 1 hour after TPA treatment, 12-fold decrease at 4 hours, undetectable levels after 8 hours and low-level expression returning at 24 hours after treatment. Down-regulated by serum stimulation, with expression levels reaching their minimum at 4 hours after stimulation and returning back to normal levels at 16 hours after stimulation. Ref.2
Disruption phenotype: Half of the embryos die by E18.5 and neonates die within an hour. Mutants display defective B-lymphopoiesis, defective myelopoiesis in the bone marrow but not in the liver, and defective formation of the heart ventricular septum. Ref.9
Sequence similarities: Belongs to the intercrine alpha (chemokine CxC) family.
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