|
|
 Previous Article | Table of Contents | Next Article 
Induction of tyrosine phosphorylation of Vav and expression of Pim-1
correlates with Jak2-mediated growth signaling from the erythropoietin
receptor
O Miura, Y Miura, N Nakamura, FW Quelle, BA Witthuhn, JN Ihle and N Aoki
First Department of Internal Medicine, Tokyo Medical and Dental University,
Japan.
The receptor for erythropoietin (Epo) belongs to the cytokine receptor
family and lacks a tyrosine kinase domain. However, it has been
hypothesized that a tyrosine kinase, Jak2, associates with the membrane
proximal cytoplasmic region of Epo receptor (EpoR) and mediates the growth
signaling from the receptor through tyrosine phosphorylation of cellular
substrates. To explore the growth signaling pathways from the EpoR, we
analyzed substrates of tyrosine phosphorylation induced by Epo stimulation
in cells expressing various mutant EpoRs. The vav proto- oncogene product
was found to be tyrosine phosphorylated after Epo stimulation in cells
expressing the wild-type EpoR or a truncated receptor, H mutant, that
retains the growth signaling function. In these cells, Epo also induced the
expression of a serine/threonine kinase, Pim-1. However, Epo stimulation
did not have any effect on Vav or Pim-1 in cells expressing a mutant EpoR,
PM4 mutant, inactivated by a point mutation, Trp282 to Arg, in the membrane
proximal region, which abrogates the interaction with Jak2. On the other
hand, both tyrosine phosphorylation of Vav and expression of Pim-1 were
observed constitutively in cells expressing a mutant EpoR that is
constitutively activated by a point mutation, Arg 129 to Cys, in the
extracellular domain. Jak2 was also constitutively tyrosine phosphorylated
and activated in cells expressing this mutant, which confirms the crucial
role of Jak2 in growth signaling from the EpoR. Taken together, these
observations suggest that the tyrosine phosphorylation of Vav and the
expression of Pim-1 may play important roles in growth signaling from the
EpoR.
Volume 84,
Issue 12,
pp. 4135-4141,
12/15/1994
Copyright © 1994 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
S. A. Didichenko, N. Spiegl, T. Brunner, and C. A. Dahinden
IL-3 induces a Pim1-dependent antiapoptotic pathway in primary human basophils
Blood,
November 15, 2008;
112(10):
3949 - 3958.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Buchse, H. Prietzsch, T. Sasse, S. Korbel, G. Stigge, S. Bogdanow, J. Brock, and T. Bittorf
Profiling of Early Gene Expression Induced by Erythropoietin Receptor Structural Variants
J. Biol. Chem.,
March 24, 2006;
281(12):
7697 - 7707.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K.-T. Kim, K. Baird, J.-Y. Ahn, P. Meltzer, M. Lilly, M. Levis, and D. Small
Pim-1 is up-regulated by constitutively activated FLT3 and plays a role in FLT3-mediated cell survival
Blood,
February 15, 2005;
105(4):
1759 - 1767.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. I. Belenkov, G. Shenouda, E. Rizhevskaya, D. Cournoyer, J.-P. Belzile, L. Souhami, S. Devic, and T. Y.K. Chow
Erythropoietin induces cancer cell resistance to ionizing radiation and to cisplatin
Mol. Cancer Ther.,
December 1, 2004;
3(12):
1525 - 1532.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Mikkers, M. Nawijn, J. Allen, C. Brouwers, E. Verhoeven, J. Jonkers, and A. Berns
Mice Deficient for All PIM Kinases Display Reduced Body Size and Impaired Responses to Hematopoietic Growth Factors
Mol. Cell. Biol.,
July 1, 2004;
24(13):
6104 - 6115.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Li, M. P. Menon, V. G. Karur, S. Hegde, and D. M. Wojchowski
Attenuated signaling by a phosphotyrosine-null Epo receptor form in primary erythroid progenitor cells
Blood,
November 1, 2003;
102(9):
3147 - 3153.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Zhu, L. M. Ramirez, R. L. Lee, N. S. Magnuson, G. A. Bishop, and M. R. Gold
CD40 Signaling in B Cells Regulates the Expression of the Pim-1 Kinase Via the NF-{kappa}B Pathway
J. Immunol.,
January 15, 2002;
168(2):
744 - 754.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. R. Bustelo
Regulatory and Signaling Properties of the Vav Family
Mol. Cell. Biol.,
March 1, 2000;
20(5):
1461 - 1477.
[Full Text]
|
|
|
|
|
|
|
J. M. Mason, B. K. Beattie, Q. Liu, D. J. Dumont, and D. L. Barber
The SH2 Inositol 5-Phosphatase Ship1 Is Recruited in an SH2-dependent Manner to the Erythropoietin Receptor
J. Biol. Chem.,
February 11, 2000;
275(6):
4398 - 4406.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Pandey, A. V. Podtelejnikov, B. Blagoev, X. R. Bustelo, M. Mann, and H. F. Lodish
Analysis of receptor signaling pathways by mass spectrometry: Identification of Vav-2 as a substrate of the epidermal and platelet-derived growth factor receptors
PNAS,
January 4, 2000;
97(1):
179 - 184.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. P. Miller, Z. Y. Liu, C. T. Noguchi, and D. M. Wojchowski
A Minimal Cytoplasmic Subdomain of the Erythropoietin Receptor Mediates Erythroid and Megakaryocytic Cell Development
Blood,
November 15, 1999;
94(10):
3381 - 3387.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Wickrema, S. Uddin, A. Sharma, F. Chen, Y. Alsayed, S. Ahmad, S. T. Sawyer, G. Krystal, T. Yi, K. Nishada, et al.
Engagement of Gab1 and Gab2 in Erythropoietin Signaling
J. Biol. Chem.,
August 27, 1999;
274(35):
24469 - 24474.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. A. Miller, D. L. Barber, L. L. Bell, B. K. Beattie, M.-Y. Zhang, B. G. Neel, M. Yoakim, L. I. Rothblum, and J. Y. Cheung
Identification of the Erythropoietin Receptor Domain Required for Calcium Channel Activation
J. Biol. Chem.,
July 16, 1999;
274(29):
20465 - 20472.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Mochizuki, C. Kitanaka, K. Noguchi, T. Muramatsu, A. Asai, and Y. Kuchino
Physical and Functional Interactions between Pim-1 Kinase and Cdc25A Phosphatase. IMPLICATIONS FOR THE Pim-1-MEDIATED ACTIVATION OF THE c-Myc SIGNALING PATHWAY
J. Biol. Chem.,
June 25, 1999;
274(26):
18659 - 18666.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. Jacobs-Helber, A. Wickrema, M. J. Birrer, and S. T. Sawyer
AP1 Regulation of Proliferation and Initiation of Apoptosis in Erythropoietin-Dependent Erythroid Cells
Mol. Cell. Biol.,
July 1, 1998;
18(7):
3699 - 3707.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
H. Chin, A. Arai, H. Wakao, R. Kamiyama, N. Miyasaka, and O. Miura
Lyn Physically Associates With the Erythropoietin Receptor and May Play a Role in Activation of the Stat5 Pathway
Blood,
May 15, 1998;
91(10):
3734 - 3745.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Chin, H. Wakao, A. Miyajima, R. Kamiyama, N. Miyasaka, and O. Miura
Erythropoietin Induces Tyrosine Phosphorylation of the Interleukin-3 Receptor beta Subunit (beta IL3 ) and Recruitment of Stat5 to Possible Stat5-Docking Sites in beta IL3
Blood,
June 15, 1997;
89(12):
4327 - 4336.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Shigematsu, H. Iwasaki, T. Otsuka, Y. Ohno, F. Arima, and Y. Niho
Role of the vav Proto-oncogene Product (Vav) in Erythropoietin-mediated Cell Proliferation and Phosphatidylinositol 3-Kinase Activity
J. Biol. Chem.,
May 30, 1997;
272(22):
14334 - 14340.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Joneja and D. M. Wojchowski
Mitogenic Signaling and Inhibition of Apoptosis via the Erythropoietin Receptor Box-1 Domain
J. Biol. Chem.,
April 25, 1997;
272(17):
11176 - 11184.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. K. Palaty, G. Kalmar, G. Tai, S. Oh, L. Amankawa, M. Affolter, R. Aebersold, and S. L. Pelech
Identification of the Autophosphorylation Sites of the Xenopus laevis Pim-1 Proto-oncogene-encoded Protein Kinase
J. Biol. Chem.,
April 18, 1997;
272(16):
10514 - 10521.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Feger, A. Dubart, C. Lacout, I. Dusanter-Fourt, P. Mayeux, W. Vainchenker, and D. Dumenil
Ectopic Expression of the Erythropoietin Receptor in a Murine Interleukin-6-Dependent Plasmacytoma Cell Line (TEPC-2027) Confers Proliferative Responsiveness to Erythropoietin
Blood,
January 15, 1997;
89(2):
435 - 445.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Nakamura, H. Chin, N. Miyasaka, and O. Miura
An Epidermal Growth Factor Receptor/Jak2 Tyrosine Kinase Domain Chimera Induces Tyrosine Phosphorylation of Stat5 and Transduces a Growth Signal in Hematopoietic Cells
J. Biol. Chem.,
August 9, 1996;
271(32):
19483 - 19488.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N Bonnefoy-Berard, A Munshi, I Yron, S Wu, T. Collins, M Deckert, T Shalom- Barak, L Giampa, E Herbert, J Hernandez, et al.
Vav: function and regulation in hematopoietic cell signaling
Stem Cells,
May 1, 1996;
14(3):
250 - 268.
[Abstract]
|
|
|
|
|
|
|
C. Guillard, S. Chretien, R. Jockers, S. Fichelson, P. Mayeux, and V. Duprez
Coupling of Heterotrimeric Gi Proteins to the Erythropoietin Receptor
J. Biol. Chem.,
January 12, 2001;
276(3):
2007 - 2014.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
