Chemokine CXCL12 Induces Binding of Ferritin Heavy Chain to the Chemokine Receptor CXCR4, Alters CXCR4 Signaling, and Induces Phosphorylation and Nuclear Translocation of Ferritin Heavy Chain *

摘要: Chemokine receptor-initiated signaling plays critical roles in cell differentiation, proliferation, and migration. However, the regulation of chemokine receptor under physiological pathological conditions is not fully understood. In present study, we demonstrate that CXC 4 (CXCR4) formed a complex with ferritin heavy chain (FHC) ligand-dependent manner. Our vitro binding assays revealed purified FHC associated both glutathione S-transferase-conjugated N-terminal C-terminal domains CXCR4, thereby suggesting presence more than one site protein sequence CXCR4. Using confocal microscopy, observed stimulation CXCL12, ligand, induced colocalization internalized CXCR4 into internal vesicles. Furthermore, after CXCL12 treatment, underwent time-dependent nuclear translocation phosphorylation at serine residues. By contrast, mutant form which 178 was replaced by alanine (S178A) failed to undergo phosphorylation, major site. Compared wild type FHC, FHC-S178A exhibited reduced association constitutive translocation. We also found CXCR4-mediated extracellular signal-regulated kinase 1/2 (ERK1/2) activation chemotaxis were inhibited overexpression but mutant, prolonged knockdown. addition other appeared be similarly regulated because CXCR2-mediated ERK1/2 Altogether, our data provide strong evidence for an important role receptor-mediated