Identification and characterization of Magmas, a novel mitochondria-associated protein involved in granulocyte-macrophage colony-stimulating factor signal transduction.
OBJECTIVE
The aim of this study was to identify granulocyte-macrophage colony-stimulating factor (GM-CSF) responsive genes.


METHODS
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.


RESULTS
A gene, named Magmas (mitochondria-associated granulocyte macrophage CSF signaling 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.


CONCLUSIONS
Magmas is a mitochondrial protein involved in GM-CSF signal transduction.
Jubinsky
P T
PT
Divisions of Hematology/Oncology, Children's Hospital Research Foundation, Cincinnati, Ohio 45229-3039, USA. jubip0@chmcc.org
Messer
A
A
Bender
J
J
Morris
R E
RE
Ciraolo
G M
GM
Witte
D P
DP
Hawley
R G
RG
Short
M K
MK
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003115:Colony-Stimulating Factors / Q000502:physiology*; D015723:Gene Library; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology*
D003115:Colony-Stimulating Factors; D012333:RNA, Messenger; D016173:Macrophage Colony-Stimulating Factor