DEK, a nuclear protein, is chemotactic for hematopoietic stem/progenitor cells acting through CXCR2 and Gαi signaling. Issue 3 (8th February 2022)

• Record Type: Journal Article
• Authors: Capitano, Maegan L; Sammour, Yasser; Ropa, James; Legendre, Maureen; Mor-Vaknin, Nirit; Markovitz, David M
• Is Part Of: Journal of leukocyte biology. Volume 112:Issue 3(2022)
• Page Start: 449
• Page End: 456
• Publication Date: 2022-02-08
• Subjects: chemokines -- chemotaxis -- CXCR2 -- DEK -- Gαi signaling -- hematopoietic stem and progenitor cells; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1002/JLB.3AB1120-740R
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract: Few cytokines/growth modulating proteins are known to be chemoattractants for hematopoietic stem (HSC) and progenitor cells (HPC); stromal cell-derived factor 1α (SDF1α/CXCL12) being the most potent known such protein. DEK, a nuclear DNA-binding chromatin protein with hematopoietic cytokine-like activity, is a chemotactic factor attracting mature immune cells. Transwell migration assays were performed to test whether DEK serves as a chemotactic agent for HSC/HPC. DEK induced dose- and time-dependent directed migration of lineage negative (Lin – ) Sca-1 + c-Kit + (LSK) bone marrow (BM) cells, HSCs and HPCs. Checkerboard assays demonstrated that DEK's activity was chemotactic (directed), not chemokinetic (random migration), in nature. DEK and SDF1α compete for HSC/HPC chemotaxis. Blocking CXCR2 with neutralizing antibodies or inhibiting Gαi protein signaling with Pertussis toxin pretreatment inhibited migration of LSK cells toward DEK. Thus, DEK is a novel and rare chemotactic agent for HSC/HPC acting in a direct or indirect CXCR2 and Gαi protein-coupled signaling-dependent manner. Graphical Abstract: The nuclear protein DEK acts as a chemotactic factor for hematopoietic stem and progenitor cells in a CXCR2- and Gαi protein-coupled signaling-dependent manner.