CXCL14 is no direct modulator of CXCR4. Issue 24 (18th November 2014)

• Record Type: Journal Article
• Authors: Otte, Maik; Kliewer, Andrea; Schütz, Dagmar; Reimann, Christiane; Schulz, Stefan; Stumm, Ralf
• Is Part Of: FEBS letters. Volume 588:Issue 24(2014)
• Page Start: 4769
• Page End: 4775
• Publication Date: 2014-11-18
• Subjects: CXCL12 -- CXCR4 -- CXCL14 -- AMD3465 -- AMD3100 -- Dynamic mass redistribution -- CXCR4 antagonist; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2014.11.009
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : C‐X‐C motif chemokine 12/C‐X‐C chemokine receptor type 4 (CXCL12/CXCR4) signaling is involved in ontogenesis, hematopoiesis, immune function and cancer. Recently, the orphan chemokine CXCL14 was reported to inhibit CXCL12‐induced chemotaxis – probably by allosteric modulation of CXCR4. We thus examined the effects of CXCL14 on CXCR4 regulation and function using CXCR4‐transfected human embryonic kidney (HEK293) cells and Jurkat T cells. CXCL14 did not affect dose–response profiles of CXCL12‐induced CXCR4 phosphorylation, G protein‐mediated calcium mobilization, dynamic mass redistribution, kinetics of extracellular signal‐regulated kinase 1 (ERK1) and ERK2 phosphorylation or CXCR4 internalization. Hence, essential CXCL12‐operated functions of CXCR4 are insensitive to CXCL14, suggesting that interactions of CXCL12 and CXCL14 pathways depend on a yet to be identified CXCL14 receptor. Abstract : CXCL14 modulation of CXCL12‐operated CXCR4 regulation and function was examined. CXCL14 had no effect on CXCL12‐induced CXCR4 phosphorylation at serines 346, 347. CXCL12‐induced dynamic mass redistribution was not changed by CXCL14. G protein and Erk1, 2 signaling of CXCR4 were also unaffected. CXCL12 should still be considered the only relevant chemokine ligand of CXCR4.