CXCL14 is no direct modulator of CXCR4

FEBS Lett. 2014 Dec 20;588(24):4769-75. doi: 10.1016/j.febslet.2014.11.009. Epub 2014 Nov 18.

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.

Keywords: AMD3100; AMD3465; CXCL12; CXCL14; CXCR4; CXCR4 antagonist; Dynamic mass redistribution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Chemokines, CXC / metabolism*
  • HEK293 Cells
  • Humans
  • Jurkat Cells
  • MAP Kinase Signaling System
  • Protein Transport
  • Receptors, CXCR4 / chemistry
  • Receptors, CXCR4 / metabolism*

Substances

  • CXCL14 protein, human
  • Chemokines, CXC
  • Receptors, CXCR4