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Erythropoietin receptor binds to Friend virus gp55 through other membrane components
1Tsukuba Life Science Center, Institute of Physical and Chemical Research (RIKEN), Ibaraki, Japan.
Abstract:
Direct interactions of Friend spleen focus-forming virus glycoprotein gp55 with either erythropoietin receptor (EpoR) or interleukin (IL)2 receptor beta chain (IL2R) (but not with IL3 receptor) have been reported to induce factor-independent prolonged proliferation of erythroid or lymphoid cells. In order to clarify the molecular mechanism by which EpoR-gp55 complex transmits an aberrant growth signal in the absence of erythropoietin, various chimeric receptors constituted with IL2R, EpoR or IL3 receptor were constructed. It was found that coexpression of gp55 and the chimeric receptors containing the cytoplasmic domains of EpoR and the extracellular domains of IL3 (or IL2) receptor in IL3-dependent Ba/F3 cells results in factor-independent growth. Since gp55 in cell membrane has only a two amino acid tail in the cytoplasmic domains and thus cannot interact with EpoR in cytoplasm, our data suggest that gp55 does not bind EpoR directly but interacts with EpoR through third membrane component(s).
Insights
Friend spleen focus-forming virus glycoprotein gp55 induces cell proliferation by interacting with erythropoietin receptor (EpoR) indirectly. This interaction involves a third membrane component, not direct binding, clarifying aberrant growth signaling.
Area of Science:
- Molecular Biology
- Virology
- Cellular Signaling
Background:
- Friend spleen focus-forming virus glycoprotein gp55 is known to induce factor-independent cell proliferation.
- Previous studies suggested direct interactions between gp55 and erythropoietin receptor (EpoR) or interleukin 2 receptor (IL2R).
Purpose of the Study:
- To elucidate the molecular mechanism of aberrant growth signaling mediated by the EpoR-gp55 complex.
- To investigate the role of specific receptor domains in gp55-induced cell proliferation.
Main Methods:
- Construction and co-expression of various chimeric receptors (IL2R, EpoR, IL3 receptor) with gp55 in IL3-dependent Ba/F3 cells.
- Analysis of factor-independent cell growth upon receptor-gp55 co-expression.
Main Results:
- Co-expression of gp55 with chimeric receptors containing EpoR cytoplasmic domains and IL3/IL2 receptor extracellular domains induced factor-independent growth in Ba/F3 cells.
- gp55 possesses a minimal two-amino acid cytoplasmic tail, precluding direct interaction with intracellular EpoR.
Conclusions:
- The interaction between gp55 and EpoR is indirect, mediated by one or more additional membrane components.
- This indirect interaction is sufficient to transmit aberrant growth signals, leading to prolonged cell proliferation.