bFGF signaling and v-Myb cooperate in sustained growth of primitive erythroid progenitors.
The development of red blood cells from hematopoietic progenitors requires the interplay of specific extracellular factors and transcriptional regulators. Here we have identified an erythroid progenitor that is critically dependent on bFGF and requires expression of AMV v-Myb for sustained proliferation in vitro, indicating that bFGF and Myb proteins cooperate in these cells. In the presence of bFGF such v-Myb cells are completely blocked in their ability to differentiate and exhibit an exceptionally high proliferative potential and long lifespan in vitro. Interestingly, in the absence of bFGF cells effectively differentiate into mature erythrocytes, irrespective of constitutive and elevated levels of v-Myb. We also demonstrate that these cells express high levels of FGF receptor type 1 (FGFR1) and that phospholipase C(gamma) (PLC(gamma)) is one of the important molecules in FGF receptor signaling. Our studies suggest that bFGF, in cooperation with Myb proteins, represents an important factor for determining erythroid lineage choice. These findings unravel a so far unidentified link between extracellular signaling and Myb in hematopoietic cells.
Bartůnek
Petr
P
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Flemingovo n. 2, 166 37 Prague 6, Czech Republic.
Pajer
Petr
P
Karafiát
Vít
V
Blendinger
Gitta
G
Dvorák
Michal
M
Zenke
Martin
M
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D002642:Chick Embryo; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015672:Erythroid Precursor Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005347:Fibroblasts; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006454:Hemoglobins / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008934:Mitogens / Q000494:pharmacology; D020626:Oncogene Proteins v-myb / Q000378:metabolism*; D051966:Phospholipase C gamma; D011506:Proteins / Q000502:physiology; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction / Q000187:drug effects; D010738:Type C Phospholipases / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D006454:Hemoglobins; D007527:Isoenzymes; D008934:Mitogens; D020626:Oncogene Proteins v-myb; D011506:Proteins; D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D055765:Shc Signaling Adaptor Proteins; D016222:Fibroblast Growth Factor 2; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D010738:Type C Phospholipases; D051966:Phospholipase C gamma