Characterization, chromosomal localization, and expression during hematopoietic differentiation of the gene encoding Arl6ip, ADP-ribosylation-like factor-6 interacting protein (ARL6)

Proliferation and differentiation of hematopoietic stem cells and progenito rs are regulated by signals from the microenvironment, involving both secre ted cytokines and adhesion molecules. The exact mechanisms by which cytokin es act on hematopoietic development are still not well understood. To exten d the molecular characterization of gene regulation during cytokine-induced hematopoiesis, we applied mRNA differential display to identify genes regu lated when multipotent progenitor cells are allowed to differentiate into m onocytes and, neutrophils, Here we report the isolation and characterizatio n of a gene that is downregulated during nnyeloid differentiation and encod es a 23-kDa protein with four putative transmembrane segments. The gene, wh ich we named Arl6ip, is identical to a mouse gene recently identified by it s physical interaction with ADP-ribosylation-like factor-6 (ARL6), belongin g to the Ras superfamily, We add information on its full-length characteriz ation as well as its regulation during hematopoiesis. It is expressed in al l hematopoietic cell lineages, but the highest level of expression is found in early myeloid progenitor cells. Preliminary studies by immunofluorescen ce microscopy revealed that; the ARL6IP protein is predominantly localized to intracytoplasmic membranes. This suggests an involvement of the Arl6ip g ene in protein transport, membrane trafficking, or cell signaling during he matopoietic maturation. (C) 2000 Academic Press.