Blood online
Home About Blood Authors Subscriptions Permission Advertising Public Access contact us
 

 
Advanced
Current Issue
First Edition
Future Articles
Archives
Submit to Blood
Search
American Society of Hematology
Meeting Abstracts
Email Alerts
This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Right arrow Rights and Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tsujimura, T
Right arrow Articles by Kanakura, Y
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tsujimura, T
Right arrow Articles by Kanakura, Y
Social Bookmarking
 Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

arrow to previous article Previous Article  |  Table of Contents  |  Next Article next article arrow

Ligand-independent activation of c-kit receptor tyrosine kinase in a murine mastocytoma cell line P-815 generated by a point mutation

T Tsujimura, T Furitsu, M Morimoto, K Isozaki, S Nomura, Y Matsuzawa, Y Kitamura and Y Kanakura

Department of Pathology, Osaka University Medical School, Japan.

The c-kit proto-oncogene encodes a receptor tyrosine kinase that is known to play a crucial role in hematopoiesis, especially in mast cell growth and differentiation. Although a number of dominant loss-of- function mutations of c-kit gene have been well characterized in mice, rats, and humans, little is known about the c-kit mutations contributing to ligand-independent activation of the c-kit receptor tyrosine kinase (KIT). In a murine mastocytoma cell line, P-815, KIT has been found to be constitutively phosphorylated on tyrosine and activated in a ligand-independent manner. Sequencing of the whole coding region of c-kit cDNA showed that c-kit cDNA of P-815 cells carries a point mutation in codon 814, resulting in amino acid substitution of Tyr for Asp. Murine wild-type c-kit cDNA and mutant- type c-kit cDNA encoding Tyr in codon 814 were expressed in cells of a human embryonic kidney cell line, 293T. In the transfected cells, mutant-form KITTyr814 was strikingly phosphorylated on tyrosine and activated in immune complex kinase reaction regardless of stimulation with a ligand for KIT (stem cell factor), whereas tyrosine phosphorylation and activation was barely detectable in wild-form KIT. The data presented here provide evidence for a novel activating mutation of c-kit gene that might be involved in neoplastic growth or oncogenesis of some cell types, including mast cells.

Volume 83, Issue 9, pp. 2619-2626, 05/01/1994
Copyright © 1994 by The American Society of Hematology


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
Mol. Cell. Biol.Home page
Z. Xiang, F. Kreisel, J. Cain, A. Colson, and M. H. Tomasson
Neoplasia Driven by Mutant c-KIT Is Mediated by Intracellular, Not Plasma Membrane, Receptor Signaling
Mol. Cell. Biol., January 1, 2007; 27(1): 267 - 282.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
A. Schirmer, J. Kennedy, S. Murli, R. Reid, and D. V. Santi
Targeted covalent inactivation of protein kinases by resorcylic acid lactone polyketides.
PNAS, March 14, 2006; 103(11): 4234 - 4239.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
M. M. Schittenhelm, S. Shiraga, A. Schroeder, A. S. Corbin, D. Griffith, F. Y. Lee, C. Bokemeyer, M. W.N. Deininger, B. J. Druker, and M. C. Heinrich
Dasatinib (BMS-354825), a Dual SRC/ABL Kinase Inhibitor, Inhibits the Kinase Activity of Wild-Type, Juxtamembrane, and Activation Loop Mutant KIT Isoforms Associated with Human Malignancies
Cancer Res., January 1, 2006; 66(1): 473 - 481.
[Abstract] [Full Text] [PDF]


Home page
JEMHome page
J. P. Zappulla, P. Dubreuil, S. Desbois, S. Letard, N. B. Hamouda, M. Daeron, G. Delsol, M. Arock, and R. S. Liblau
Mastocytosis in mice expressing human Kit receptor with the activating Asp816Val mutation
J. Exp. Med., December 19, 2005; 202(12): 1635 - 1641.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
A. Tanaka, M. Konno, S. Muto, N. Kambe, E. Morii, T. Nakahata, A. Itai, and H. Matsuda
A novel NF-{kappa}B inhibitor, IMD-0354, suppresses neoplastic proliferation of human mast cells with constitutively activated c-kit receptors
Blood, March 15, 2005; 105(6): 2324 - 2331.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Pathol.Home page
A. Okaya, J. Kitanaka, N. Kitanaka, M. Satake, Y. Kim, K. Terada, T. Sugiyama, M. Takemura, J. Fujimoto, N. Terada, et al.
Oncostatin M Inhibits Proliferation of Rat Oval Cells, OC15-5, Inducing Differentiation into Hepatocytes
Am. J. Pathol., March 1, 2005; 166(3): 709 - 719.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
T. Jelacic and D. Linnekin
PKC{delta} plays opposite roles in growth mediated by wild-type Kit and an oncogenic Kit mutant
Blood, March 1, 2005; 105(5): 1923 - 1929.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
P. Chen, M. Levis, P. Brown, K.-T. Kim, J. Allebach, and D. Small
FLT3/ITD Mutation Signaling Includes Suppression of SHP-1
J. Biol. Chem., February 18, 2005; 280(7): 5361 - 5369.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
S. R. Gillespie, R. R. DeMartino, J. Zhu, H. J. Chong, C. Ramirez, C. P. Shelburne, L. A. Bouton, D. P. Bailey, A. Gharse, P. Mirmonsef, et al.
IL-10 Inhibits Fc{epsilon}RI Expression in Mouse Mast Cells
J. Immunol., March 1, 2004; 172(5): 3181 - 3188.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
K. Hashimoto, I. Matsumura, T. Tsujimura, D.-K. Kim, H. Ogihara, H. Ikeda, S. Ueda, M. Mizuki, H. Sugahara, H. Shibayama, et al.
Necessity of tyrosine 719 and phosphatidylinositol 3'-kinase-mediated signal pathway in constitutive activation and oncogenic potential of c-kit receptor tyrosine kinase with the Asp814Val mutation
Blood, February 1, 2003; 101(3): 1094 - 1102.
[Abstract] [Full Text] [PDF]


Home page
Molecular Cancer TherapeuticsHome page
M. J. Frost, P. T. Ferrao, T. P. Hughes, and L. K. Ashman
Juxtamembrane Mutant V560GKit Is More Sensitive to Imatinib (STI571) Compared with Wild-Type c-Kit Whereas the Kinase Domain Mutant D816VKit Is Resistant
Mol. Cancer Ther., October 1, 2002; 1(12): 1115 - 1124.
[Abstract] [Full Text] [PDF]


Home page
Vet PatholHome page
D. Zemke, B. Yamini, and V. Yuzbasiyan-Gurkan
Mutations in the Juxtamembrane Domain of c-KIT Are Associated with Higher Grade Mast Cell Tumors in Dogs
Vet. Pathol., September 1, 2002; 39(5): 529 - 535.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
A. T. Liao, M. B. Chien, N. Shenoy, D. B. Mendel, G. McMahon, J. M. Cherrington, and C. A. London
Inhibition of constitutively active forms of mutant kit by multitargeted indolinone tyrosine kinase inhibitors
Blood, June 28, 2002; 100(2): 585 - 593.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
N. Anzai, Y. Lee, B.-S. Youn, S. Fukuda, Y.-J. Kim, C. Mantel, M. Akashi, and H. E. Broxmeyer
c-kit associated with the transmembrane 4 superfamily proteins constitutes a functionally distinct subunit in human hematopoietic progenitors
Blood, May 29, 2002; 99(12): 4413 - 4421.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
Y. Ma, S. Zeng, D. D. Metcalfe, C. Akin, S. Dimitrijevic, J. H. Butterfield, G. McMahon, and B. J. Longley
The c-KIT mutation causing human mastocytosis is resistant to STI571 and other KIT kinase inhibitors; kinases with enzymatic site mutations show different inhibitor sensitivity profiles than wild-type kinases and those with regulatory-type mutations
Blood, March 1, 2002; 99(5): 1741 - 1744.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
B. P. Rubin, S. Singer, C. Tsao, A. Duensing, M. L. Lux, R. Ruiz, M. K. Hibbard, C.-J. Chen, S. Xiao, D. A. Tuveson, et al.
KIT Activation Is a Ubiquitous Feature of Gastrointestinal Stromal Tumors
Cancer Res., November 1, 2001; 61(22): 8118 - 8121.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
R. Chian, S. Young, A. Danilkovitch-Miagkova, L. Ronnstrand, E. Leonard, P. Ferrao, L. Ashman, and D. Linnekin
Phosphatidylinositol 3 kinase contributes to the transformation of hematopoietic cells by the D816V c-Kit mutant
Blood, September 1, 2001; 98(5): 1365 - 1373.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
M. L. Taylor, J. Dastych, D. Sehgal, M. Sundstrom, G. Nilsson, C. Akin, R. G. Mage, and D. D. Metcalfe
The Kit-activating mutation D816V enhances stem cell factor-dependent chemotaxis
Blood, August 15, 2001; 98(4): 1195 - 1199.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
Z.-Q. Ning, J. Li, and R. J. Arceci
Signal transducer and activator of transcription 3 activation is required for Asp816 mutant c-Kit-mediated cytokine-independent survival and proliferation in human leukemia cells
Blood, June 1, 2001; 97(11): 3559 - 3567.
[Abstract] [Full Text] [PDF]


Home page
JEMHome page
C. F. Yeatman , II, S. M. Jacobs-Helber, P. Mirmonsef, S. R. Gillespie, L. A. Bouton, H. A. Collins, S. T. Sawyer, C. P. Shelburne, and J. J. Ryan
Combined Stimulation with the T Helper Cell Type 2 Cytokines Interleukin (IL)-4 and IL-10 Induces Mouse Mast Cell Apoptosis
J. Exp. Med., October 9, 2000; 192(8): 1093 - 1104.
[Abstract] [Full Text] [PDF]


Home page
JEMHome page
J. Kitaura, K. Asai, M. Maeda-Yamamoto, Y. Kawakami, U. Kikkawa, and T. Kawakami
Akt-dependent Cytokine Production in Mast Cells
J. Exp. Med., September 5, 2000; 192(5): 729 - 740.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
T. Hongyo, T. Li, M. Syaifudin, R. Baskar, H. Ikeda, Y. Kanakura, K. Aozasa, and T. Nomura
Specific c-kit Mutations in Sinonasal Natural Killer/T-Cell Lymphoma in China and Japan
Cancer Res., May 1, 2000; 60(9): 2345 - 2347.
[Abstract] [Full Text]


Home page
Am. J. Pathol.Home page
M. L. Lux, B. P. Rubin, T. L. Biase, C.-J. Chen, T. Maclure, G. Demetri, S. Xiao, S. Singer, C. D.M. Fletcher, and J. A. Fletcher
KIT Extracellular and Kinase Domain Mutations in Gastrointestinal Stromal Tumors
Am. J. Pathol., March 1, 2000; 156(3): 791 - 795.
[Abstract] [Full Text] [PDF]


Home page
INT J SURG PATHOLHome page
B. P. Rubin, J. A. Fletcher, and C. D. M. Fletcher
Molecular Insights into the Histogenesis and Pathogenesis of Gastrointestinal Stromal Tumors
International Journal of Surgical Pathology, January 1, 2000; 8(1): 5 - 10.
[Abstract] [PDF]


Home page
BloodHome page
A. Tanaka, K. Arai, Y. Kitamura, and H. Matsuda
Matrix Metalloproteinase-9 Production, a Newly Identified Function of Mast Cell Progenitors, Is Downregulated by c-kit Receptor Activation
Blood, October 1, 1999; 94(7): 2390 - 2395.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
O. Malbec, W. H. Fridman, and M. Daeron
Negative Regulation of c-kit-Mediated Cell Proliferation by Fc{gamma}RIIB
J. Immunol., April 15, 1999; 162(8): 4424 - 4429.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
B. J. Longley Jr., D. D. Metcalfe, M. Tharp, X. Wang, L. Tyrrell, S.-z. Lu, D. Heitjan, and Y. Ma
Activating and dominant inactivating c-KIT catalytic domain mutations in distinct clinical forms of human mastocytosis
PNAS, February 16, 1999; 96(4): 1609 - 1614.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
T. Tsujimura, K. Hashimoto, H. Kitayama, H. Ikeda, H. Sugahara, I. Matsumura, T. Kaisho, N. Terada, Y. Kitamura, and Y. Kanakura
Activating Mutation in the Catalytic Domain of c-kit Elicits Hematopoietic Transformation by Receptor Self-Association Not at the Ligand-Induced Dimerization Site
Blood, February 15, 1999; 93(4): 1319 - 1329.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
N. R. Leslie, J. O'Prey, C. Bartholomew, and P. R. Harrison
An Activating Mutation in the Kit Receptor Abolishes the Stroma Requirement for Growth of ELM Erythroleukemia Cells, But Does Not Prevent Their Differentiation in Response to Erythropoietin
Blood, December 15, 1998; 92(12): 4798 - 4807.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
L. H. McKinlay, M. J. Tymms, R. S. Thomas, A. Seth, S. Hasthorpe, P. J. Hertzog, and I. Kola
The Role of Ets-1 in Mast Cell Granulocyte-Macrophage Colony-Stimulating Factor Expression and Activation
J. Immunol., October 15, 1998; 161(8): 4098 - 4105.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
A. Beghini, L. Larizza, R. Cairoli, and E. Morra
c-kit Activating Mutations and Mast Cell Proliferation in Human Leukemia
Blood, July 15, 1998; 92(2): 701 - 703.
[Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
M. Kozlowski, L. Larose, F. Lee, D. M. Le, R. Rottapel, and K. A. Siminovitch
SHP-1 Binds and Negatively Modulates the c-Kit Receptor by Interaction with Tyrosine 569 in the c-Kit Juxtamembrane Domain
Mol. Cell. Biol., April 1, 1998; 18(4): 2089 - 2099.
[Abstract] [Full Text]


Home page
BloodHome page
J. L. Gommerman and S. A. Berger
Protection From Apoptosis by Steel Factor But Not Interleukin-3 Is Reversed Through Blockade of Calcium Influx
Blood, March 15, 1998; 91(6): 1891 - 1900.
[Abstract] [Full Text] [PDF]


Home page
ScienceHome page
S. Hirota, K. Isozaki, Y. Moriyama, K. Hashimoto, T. Nishida, S. Ishiguro, K. Kawano, M. Hanada, A. Kurata, M. Takeda, et al.
Gain-of-Function Mutations of c-kit in Human Gastrointestinal Stromal Tumors
Science, January 23, 1998; 279(5350): 577 - 580.
[Abstract] [Full Text]


Home page
BloodHome page
P. Ferrao, T. J. Gonda, and L. K. Ashman
Expression of Constitutively Activated Human c-Kit in Myb Transformed Early Myeloid Cells Leads to Factor Independence, Histiocytic Differentiation, and Tumorigenicity
Blood, December 1, 1997; 90(11): 4539 - 4552.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
B. Joneja, H.-C. Chen, D. Seshasayee, A. L. Wrentmore, and D. M. Wojchowski
Mechanisms of Stem Cell Factor and Erythropoietin Proliferative Co-signaling in FDC2-ER Cells
Blood, November 1, 1997; 90(9): 3533 - 3545.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
V. C. Broudy
Stem Cell Factor and Hematopoiesis
Blood, August 15, 1997; 90(4): 1345 - 1364.
[Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
X. Piao, R. Paulson, P. van der Geer, T. Pawson, and A. Bernstein
Oncogenic mutation in the Kit receptor tyrosine kinase alters substrate specificity and induces degradation of the protein tyrosine phosphatase SHP-1
PNAS, December 10, 1996; 93(25): 14665 - 14669.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
Y. Moriyama, T. Tsujimura, K. Hashimoto, M. Morimoto, H. Kitayama, Y. Matsuzawa, Y. Kitamura, and Y. Kanakura
Role of Aspartic Acid 814 in the Function and Expression of c-kit Receptor Tyrosine Kinase
J. Biol. Chem., February 16, 1996; 271(7): 3347 - 3350.
[Abstract] [Full Text] [PDF]


Home page
Cold Spring Harb Symp Quant BiolHome page
H.F. Lodish, D.J. Hilton, U. Klingmuller, S.S. Watowich, and H. Wu
The Erythropoietin Receptor: Biogenesis, Dimerization, and Intracellular Signal Transduction
Cold Spring Harb Symp Quant Biol, January 1, 1995; 60(0): 93 - 104.
[Abstract] [PDF]



 click for free articles
home about blood authors subscriptions permissions advertising public access contact us
  Copyright © 1994 by American Society of Hematology         Online ISSN: 1528-0020