Identification and characterization of Magmas, a novel mitochondria-associated protein involved in granulocyte-macrophage colony-stimulating factor signal transduction

• Published in: Experimental hematology Vol. 29; no. 12; pp. 1392 - 1402
• Main Authors: Jubinsky, Paul T, Messer, Angela, Bender, Jeremy, Morris, Randal E, Ciraolo, Georgianne M, Witte, David P, Hawley, Robert G, Short, Mary K
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.12.2001
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Cell Line; Colony-Stimulating Factors - physiology; Gene Library; Humans; Macrophage Colony-Stimulating Factor - pharmacology; Mice; Molecular Sequence Data; RNA, Messenger - genetics; Sequence Alignment; Signal Transduction - physiology
• ISSN: 0301-472X; 1873-2399
• DOI: 10.1016/S0301-472X(01)00749-4

The aim of this study was to identify granulocyte-macrophage colony-stimulating factor (GM-CSF) responsive genes. Potential GM-CSF responsive genes were identified by comparing the mRNA expression pattern of the murine myeloid cell line PGMD1 grown in either interleukin-3 (IL-3) or GM-CSF by differential display. Human and murine cDNA clones of one of the bands having increased expression in GM-CSF were isolated. mRNA expression of the gene was examined by Northern blot. Immunohistochemistry and studies with a green fluorescent fusion protein were used to determine its intracellular location. Growth factor-stimulated proliferation of PGMD1 cells transfected with constitutively expressed sense and anti-sense cDNA constructs of the gene was measured by 3H-thymidine incorporation. A gene, named Magmas ( m itochondria- a ssociated g ranulocyte m acrophage CSF s ignaling molecule), was shown to be rapidly induced when cells were switched from IL-3 to GM-CSF. Analysis of the amino acid sequence of Magmas showed it contained a mitochondrial signal peptide, but not any other known functional domains. The human and murine clones encode nearly identical 13-kDa proteins that localized to the mitochondria. Magmas mRNA expression was observed in all tissues examined. PGMD1 cells that overexpressed Magmas proliferated similarly to untransfected cells when cultured in IL-3 or GM-CSF. In contrast, cells with reduced protein levels grew normally in IL-3, but had impaired proliferation in GM-CSF. Magmas is a mitochondrial protein involved in GM-CSF signal transduction.