Molecular cloning of the chicken myelomonocytic growth factor (cMGF) reveals relationship to interleukin 6 and granulocyte colony stimulating factor.
Normal as well as retrovirally transformed avian myeloid precursor cells require the colony stimulating factor cMGF for their survival, proliferation and colony formation in vitro. cMGF has been shown to be a glycoprotein which is active in the picomolar concentration range. Co-expression of kinase type oncogenes in v-myb or v-myc transformed myeloid cells induces cMGF expression and confers factor independence via an autocrine mechanism. Here we describe the molecular cloning of cMGF from a myeloblast cDNA library and show that it is a 201 amino acid residue secretory protein which is modified by signal peptide cleavage and glycosylation during translocation into the lumen of membrane vesicles. A bacterially expressed trpE-cMGF fusion protein induces proliferation of E26 transformed myeloblasts in a cMGF bioassay suggesting that glycosylation is not absolutely necessary for biological activity. Sequence comparison reveals that cMGF is distantly related to G-CSF and IL-6.
Leutz
A
A
European Molecular Biology Laboratory, Heidelberg, FRG.
Damm
K
K
Sterneck
E
E
Kowenz
E
E
Ness
S
S
Frank
R
R
Gausepohl
H
H
Pan
Y C
YC
Smart
J
J
Hayman
M
M
D000595:Amino Acid Sequence; D000818:Animals; D030161:Avian Proteins; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002645:Chickens / Q000235:genetics*; D003115:Colony-Stimulating Factors / Q000235:genetics; D016207:Cytokines; D004247:DNA / Q000235:genetics; D006133:Growth Substances / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D007378:Interleukins / Q000235:genetics; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000494:pharmacology; D012689:Sequence Homology, Nucleic Acid; D014407:Tumor Cells, Cultured / Q000187:drug effects
D030161:Avian Proteins; D003115:Colony-Stimulating Factors; D016207:Cytokines; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D007378:Interleukins; C059626:MGF protein, chicken; D011993:Recombinant Fusion Proteins; D004247:DNA