|
J Biol Chem, Vol. 274, Issue 13, 8669-8677, March 26, 1999
A Cell Type-specific Constitutive Point Mutant of the Common
-Subunit of the Human Granulocyte-Macrophage Colony-stimulating
Factor (GM-CSF), Interleukin (IL)-3, and IL-5 Receptors Requires the
GM-CSF Receptor -Subunit for Activation
Brendan J.
Jenkins,
Fei
Le, and
Thomas J.
Gonda
From the Hanson Centre for Cancer Research and Division of Human
Immunology, Institute of Medical and Veterinary Science, Frome Road,
Adelaide, South Australia 5000, Australia
The high affinity receptor for human
granulocyte-macrophage colony-stimulating factor (GM-CSF) consists of a
cytokine-specific -subunit (hGMR ) and a common signal-transducing
-subunit (h c) that is shared with the interleukin-3 and -5 receptors. We have previously identified a constitutively active
extracellular point mutant of h c, I374N, that can confer factor
independence on murine FDC-P1 cells but not BAF-B03 or CTLL-2 cells
(Jenkins, B. J., D'Andrea, R. J., and Gonda, T. J. (1995) EMBO J. 14, 4276-4287). This restricted activity
suggested the involvement of cell type-specific signaling molecules in
the activation of this mutant. We report here that one such molecule is
the mouse GMR (mGMR ) subunit, since introduction of mGMR , but
not hGMR , into BAF-B03 or CTLL-2 cells expressing the I374N mutant
conferred factor independence. Experiments utilizing mouse/human
chimeric GMR subunits indicated that the species specificity lies in
the extracellular domain of GMR . Importantly, the requirement for
mGMR correlated with the ability of I374N (but not wild-type h c)
to constitutively associate with mGMR . Expression of I374N in human
factor-dependent UT7 cells also led to factor-independent
proliferation, with concomitant up-regulation of hGMR surface
expression. Taken together, these findings suggest a critical role for
association with GMR in the constitutive activity of I374N.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

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

|
 |

|
 |
 
V. T. Phan, D. B. Shultz, B.-T. H. Truong, T. J. Blake, A. L. Brown, T. J. Gonda, M. M. Le Beau, and S. C. Kogan
Cooperation of Cytokine Signaling with Chimeric Transcription Factors in Leukemogenesis: PML-Retinoic Acid Receptor Alpha Blocks Growth Factor-Mediated Differentiation
Mol. Cell. Biol.,
July 1, 2003;
23(13):
4573 - 4585.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. J. Blake, B. J. Jenkins, R. J. D'Andrea, and T. J. Gonda
Functional cross-talk between cytokine receptors revealed by activating mutations in the extracellular domain of the {beta}-subunit of the GM-CSF receptor
J. Leukoc. Biol.,
December 1, 2002;
72(6):
1246 - 1255.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. McClure, F. Stomski, A. Lopez, and J. Woodcock
Perverted responses of the human granulocyte-macrophage colony-stimulating factor receptor in mouse cell lines due to cross-species beta -subunit association
Blood,
November 15, 2001;
98(10):
3165 - 3168.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Le, F. Stomski, J. M. Woodcock, A. F. Lopez, and T. J. Gonda
The Role of Disulfide-linked Dimerization in Interleukin-3 Receptor Signaling and Biological Activity
J. Biol. Chem.,
February 18, 2000;
275(7):
5124 - 5130.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. P. McCormack and T. J. Gonda
Novel murine myeloid cell lines that exhibit a differentiation switch in response to IL-3 or GM-CSF, or to different constitutively active mutants of the GM-CSF receptor beta subunit
Blood,
January 1, 2000;
95(1):
120 - 127.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 1999 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|