title: CXCL14 is no direct modulator of CXCR4.
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.
authors.affiliation: Institute of Pharmacology and Toxicology, University Hospital, Friedrich-Schiller University Jena, Germany.
authors.forename: Maik
authors.initials: M
authors.lastname: Otte
authors.affiliation: Institute of Pharmacology and Toxicology, University Hospital, Friedrich-Schiller University Jena, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kliewer
authors.affiliation: Institute of Pharmacology and Toxicology, University Hospital, Friedrich-Schiller University Jena, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Schütz
authors.affiliation: Institute of Pharmacology and Toxicology, University Hospital, Friedrich-Schiller University Jena, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Reimann
authors.affiliation: Institute of Pharmacology and Toxicology, University Hospital, Friedrich-Schiller University Jena, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schulz
authors.affiliation: Institute of Pharmacology and Toxicology, University Hospital, Friedrich-Schiller University Jena, Germany. Electronic address: Ralf.stumm@med.uni-jena.de.
authors.forename: Ralf
authors.initials: R
authors.lastname: Stumm
mesh_terms: D000595:Amino Acid Sequence; D019743:Chemokines, CXC / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D019169:Jurkat Cells; D020935:MAP Kinase Signaling System; D021381:Protein Transport; D019718:Receptors, CXCR4 / Q000737:chemistry / Q000378:metabolism*
chemical_list: C118056:CXCL14 protein, human; D019743:Chemokines, CXC; D019718:Receptors, CXCR4
keywords: AMD3100; AMD3465; CXCL12; CXCL14; CXCR4; CXCR4 antagonist; Dynamic mass redistribution