|
Volume 272, Number 14,
Issue of April 4, 1997
pp. 9099-9107
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
Cell Surface Organization of the Erythropoietin Receptor Complex
Differs Depending on its Mode of Activation
(Received for publication, September 25, 1996, and in revised form, December 23, 1996)
Kathleen
Tarr
,
Stephanie S.
Watowich
§
and
Gregory D.
Longmore
¶
From the Departments of Medicine and ¶ Cell
Biology, Washington University School of Medicine,
St. Louis, Missouri 63110 and § Department of Immunology,
M. D. Anderson Cancer Center, Houston, Texas 77030
During erythroid development erythropoietin (EPO)
binds specifically to a receptor primarily present on committed
erythroid progenitors, stimulating mitogenic, survival, and
differentiative growth response pathways. Other modes of erythropoietin
receptor (EPO-R) activation, such as interaction with the
env gene Friend virus envelope glycoprotein (F-gp55) of
spleen focus-forming virus or specific mutations in the extracellular
domain of the EPO-R, give rise to pathological consequences, in
vivo and EPO-independent proliferation and differentiation of
cultured cells. Activating extracellular receptor mutations result
in covalently linked receptor homodimers. These observations and others
have led to the proposal that EPO activates the EPO-R by inducing dimer
formation on the cell surface. It has been assumed that F-gp55 also
induces dimer formation of the EPO-R; however, clear evidence of this
is lacking. In addition, EPO and F-gp55 stimulation of the EPO-R elicit
different biological responses. To probe whether the cell surface EPO-R is structurally different with these activators, we contrasted the cell
surface EPO-R complex formed following receptor activation by EPO,
F-gp55, and mutations in the extracellular domain of the receptor. Our
results indicate that cell surface forms of activated EPO-R differ, as
judged by their differential association with F-gp55 and pattern of
associated cell surface proteins. Interestingly, we find that the
env gene of an anemic strain of Friend virus, Rauscher
virus envelope glycoprotein, does not interact with the EPO-R at the
cell surface. Thus, the mode of Rauscher virus envelope glycoprotein-induced erythroblastosis may be distinct from
F-gp55-induced erythroblastosis and possibly not involve the EPO-R.

CiteULike Complore Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
W. Ruan, V. Becker, U. Klingmuller, and D. Langosch
The Interface between Self-assembling Erythropoietin Receptor Transmembrane Segments Corresponds to a Membrane-spanning Leucine Zipper
J. Biol. Chem.,
January 30, 2004;
279(5):
3273 - 3279.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. N. Constantinescu, T. Keren, W. P. Russ, I. Ubarretxena-Belandia, Y. Malka, K. F. Kubatzky, D. M. Engelman, H. F. Lodish, and Y. I. Henis
The Erythropoietin Receptor Transmembrane Domain Mediates Complex Formation with Viral Anemic and Polycythemic gp55 Proteins
J. Biol. Chem.,
October 31, 2003;
278(44):
43755 - 43763.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Naranda, R. I. Kaufman, J. Li, K. Wong, A. Boge, D. Hallen, K. Y. C. Fung, M. W. Duncan, N. Andersen, A. Goldstein, et al.
Activation of Erythropoietin Receptor through a Novel Extracellular Binding Site
Endocrinology,
June 1, 2002;
143(6):
2293 - 2302.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. A. Ney and A. D. D'Andrea
Friend erythroleukemia revisited
Blood,
December 1, 2000;
96(12):
3675 - 3680.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Gurezka, R. Laage, B. Brosig, and D. Langosch
A Heptad Motif of Leucine Residues Found in Membrane Proteins Can Drive Self-assembly of Artificial Transmembrane Segments
J. Biol. Chem.,
April 2, 1999;
274(14):
9265 - 9270.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. S. Watowich, K. D. Liu, X. Xie, S. Y. Lai, A. Mikami, G. D. Longmore, and M. A. Goldsmith
Oligomerization and Scaffolding Functions of the Erythropoietin Receptor Cytoplasmic Tail
J. Biol. Chem.,
February 26, 1999;
274(9):
5415 - 5421.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. N. Constantinescu, H. Wu, X. Liu, W. Beyer, A. Fallon, and H. F. Lodish
The Anemic Friend Virus gp55 Envelope Protein Induces Erythroid Differentiation in Fetal Liver Colony-Forming Units-Erythroid
Blood,
February 15, 1998;
91(4):
1163 - 1172.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 1997 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|