|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 93 No. 4 (February 15), 1999:
pp. 1338-1345
GCKR Links the Bcr-Abl Oncogene and Ras to the
Stress-Activated Protein Kinase Pathway
Chong-Shan Shi,
Joseph M. Tuscano,
Owen N. Witte, and
John H. Kehrl
From the B-Cell Molecular Immunology Section, Laboratory of
Immunoregulation, National Institutes of Allergy and Infectious
Diseases, NIH, Bethesda, MD; UC Davis Cancer Center, Department of
Oncology, Sacramento, CA; University of California Los Angeles, Howard
Hughes Medical Institute, Los Angeles, CA.
The Bcr-Abl oncogene, found in Philadelphia
chromosome-positive myelogenous leukemia (CML), activates Ras and
triggers the stress-activated protein kinase (SAPK or Jun
NH2-terminal kinase [JNK]) pathway. Interruption of Ras
or SAPK activation dramatically reduces Bcr-Abl-mediated
transformation. Here, we report that Bcr-Abl through a Ras-dependent
pathway signals the serine/threonine protein kinase GCKR (Germinal
Center Kinase Related) leading to SAPK activation. Either an oncogenic
form of Ras or Bcr-Abl enhances GCKR catalytic activity and its
activation of SAPK, whereas inhibition of GCKR impairs Bcr-Abl-induced
SAPK activation. Bcr-Abl mutants that are impaired for GCKR activation
are also unable to activate SAPK. Consistent with GCKR being a
functional target in CML, GCKR is constitutively active in CML cell
lines and found in association with Bcr-Abl. Our results indicate that
GCKR is a downstream target of Bcr-Abl and strongly implicate GCKR as a
mediator of Bcr-Abl in its transformation of cells.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
J. M. Goldman and J. V. Melo
Chronic Myeloid Leukemia -- Advances in Biology and New Approaches to Treatment
N. Engl. J. Med.,
October 9, 2003;
349(15):
1451 - 1464.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Selleri, J. P. Maciejewski, N. Montuori, P. Ricci, V. Visconte, B. Serio, L. Luciano, and B. Rotoli
Involvement of nitric oxide in farnesyltransferase inhibitor-mediated apoptosis in chronic myeloid leukemia cells
Blood,
August 15, 2003;
102(4):
1490 - 1498.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Mukhopadhyay, S. Shishodia, J. Suttles, K. Brittingham, B. Lamothe, R. Nimmanapalli, K. N. Bhalla, and B. B. Aggarwal
Ectopic Expression of Protein-tyrosine Kinase Bcr-Abl Suppresses Tumor Necrosis Factor (TNF)-induced NF-kappa B Activation and Ikappa Balpha Phosphorylation. RELATIONSHIP WITH DOWN-REGULATION OF TNF RECEPTORS
J. Biol. Chem.,
August 16, 2002;
277(34):
30622 - 30628.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Hemmeryckx, A. van Wijk, A. Reichert, V. Kaartinen, Ron de Jong, P. K. Pattengale, I. Gonzalez-Gomez, J. Groffen, and N. Heisterkamp
Crkl Enhances Leukemogenesis in BCR/ABL P190 Transgenic Mice
Cancer Res.,
February 1, 2001;
61(4):
1398 - 1405.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
M. W. N. Deininger, J. M. Goldman, and J. V. Melo
The molecular biology of chronic myeloid leukemia
Blood,
November 15, 2000;
96(10):
3343 - 3356.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. H. S. Kabarowski and O. N. Witte
Consequences of BCR-ABL Expression within the Hematopoietic Stem Cell in Chronic Myeloid Leukemia
Stem Cells,
November 1, 2000;
18(6):
399 - 408.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
T. M. Moore, R. Garg, C. Johnson, M. J. Coptcoat, A. J. Ridley, and J. D. H. Morris
PSK, a Novel STE20-like Kinase Derived from Prostatic Carcinoma That Activates the c-Jun N-terminal Kinase Mitogen-activated Protein Kinase Pathway and Regulates Actin Cytoskeletal Organization
J. Biol. Chem.,
February 11, 2000;
275(6):
4311 - 4322.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C.-S. Shi, J. Tuscano, and J. H. Kehrl
Adaptor proteins CRK and CRKL associate with the serine/threonine protein kinase GCKR promoting GCKR and SAPK activation
Blood,
February 1, 2000;
95(3):
776 - 782.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
