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Identification of CRKL as the constitutively phosphorylated 39-kD tyrosine
phosphoprotein in chronic myelogenous leukemia cells
GL Nichols, MA Raines, JC Vera, L Lacomis, P Tempst and DW Golde
Division of Hematologic Oncology, Memorial Sloan-Kettering Cancer Center,
New York, NY.
Chronic myelogenous leukemia (CML) is characterized by the presence of the
Philadelphia (Ph) chromosome in clonally derived hematopoietic precursors
and their progeny. The Ph chromosome arises from a translocation that
deregulates the c-ABL protein tyrosine kinase, giving it transforming
potential and increased kinase activity. We observed a unique 39-kD
tyrosine phosphoprotein (pp39), previously reported in blastic CML cell
lines, in neutrophils from 50 cases of chronic phase CML. This protein was
prominently and constitutively tyrosine-phosphorylated in CML neutrophils
and was not phosphorylated in normal neutrophils. Stimulation of normal
neutrophils with cytokines and agonists did not induce tyrosine
phosphorylation of proteins migrating in the region of pp39, and the
phosphorylation state of pp39 in CML neutrophils was not affected by kinase
inhibitors known to downregulate the ABL kinase. The pp39 was not
phosphorylated in hematopoietic cells from healthy donors or from patients
with Ph chromosome-negative myeloproliferative disorders. Using micro amino
acid sequencing of purified preparations of pp39, we identified pp39 as
CRKL protein, which is consistent with recent immunologic studies in the
blastic K562 cell line. Immunoblotting with anti-CRKL antibodies showed the
presence of CRKL protein in CML cells and cell lines as well as in
antiphosphotyrosine immunoprecipitates from CML cells. Our results suggest
that pp39 CRKL in CML neutrophils may be stably tyrosine-phosphorylated by
the BCR/ABL kinase at an early stage of myeloid differentiation when the
ABL kinase is active. CRK, CRKL, and other SH2 (SRC homology
domain)/SH3-containing proteins function as adaptor molecules in
nonreceptor tyrosine kinase signalling pathways. Although the CRKL protein
is present in normal neutrophils, it is not tyrosine-phosphorylated, and
the inability to induce such phosphorylation in normal neutrophils suggests
a special role of this phosphoprotein in the pathogenesis of CML.
Constitutive phosphorylation of CRKL is unique to CML, indicating that it
may be a useful target for therapeutic intervention.
Volume 84,
Issue 9,
pp. 2912-2918,
11/01/1994
Copyright © 1994 by The American Society of Hematology
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112(13):
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12(23):
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Identification of 12/15-lipoxygenase as a suppressor of myeloproliferative disease
J. Exp. Med.,
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203(11):
2529 - 2540.
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|
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Dasatinib (BMS-354825) targets an earlier progenitor population than imatinib in primary CML but does not eliminate the quiescent fraction
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June 1, 2006;
107(11):
4532 - 4539.
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N. C. Wolff, D. R. Veach, W. P. Tong, W. G. Bornmann, B. Clarkson, and R. L. Ilaria Jr
PD166326, a novel tyrosine kinase inhibitor, has greater antileukemic activity than imatinib mesylate in a murine model of chronic myeloid leukemia
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May 15, 2005;
105(10):
3995 - 4003.
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|
|
|
|
|
|
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J. C. Sitko, C. I. Guevara, and N. A. Cacalano
Tyrosine-phosphorylated SOCS3 Interacts with the Nck and Crk-L Adapter Proteins and Regulates Nck Activation
J. Biol. Chem.,
September 3, 2004;
279(36):
37662 - 37669.
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[Full Text]
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|
|
|
|
|
|
|
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Combination of rapamycin and protein tyrosine kinase (PTK) inhibitors for the treatment of leukemias caused by oncogenic PTKs
PNAS,
March 2, 2004;
101(9):
3130 - 3135.
[Abstract]
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|
|
|
|
|
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J. M. Golas, K. Arndt, C. Etienne, J. Lucas, D. Nardin, J. Gibbons, P. Frost, F. Ye, D. H. Boschelli, and F. Boschelli
SKI-606, a 4-Anilino-3-quinolinecarbonitrile Dual Inhibitor of Src and Abl Kinases, Is a Potent Antiproliferative Agent against Chronic Myelogenous Leukemia Cells in Culture and Causes Regression of K562 Xenografts in Nude Mice
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63(2):
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[Abstract]
[Full Text]
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|
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|
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Blood,
September 26, 2002;
100(8):
3041 - 3044.
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|
|
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J. J. Smith, D. A. Richardson, J. Kopf, M. Yoshida, R. E. Hollingsworth, and S. Kornbluth
Apoptotic Regulation by the Crk Adapter Protein Mediated by Interactions with Wee1 and Crm1/Exportin
Mol. Cell. Biol.,
March 1, 2002;
22(5):
1412 - 1423.
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|
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N. C. Wolff and R. L. Ilaria Jr
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November 1, 2001;
98(9):
2808 - 2816.
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September 1, 2001;
98(5):
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97(12):
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|
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|
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|
|
|
|
|
|
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|
|
|
|
|
|
|
N. Uemura and J. D. Griffin
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|
|
|
|
|
|
|
Y. Nosaka, A. Arai, N. Miyasaka, and O. Miura
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274(42):
30154 - 30162.
[Abstract]
[Full Text]
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|
|
|
|
|
|
|
X. Zou and K. Calame
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J. Biol. Chem.,
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274(26):
18141 - 18144.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Arai, Y. Nosaka, H. Kohsaka, N. Miyasaka, and O. Miura
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Blood,
June 1, 1999;
93(11):
3713 - 3722.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. L. Sawyers
Chronic Myeloid Leukemia
N. Engl. J. Med.,
April 29, 1999;
340(17):
1330 - 1340.
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Ling, Z. Yao, C. F. Meyer, X. S. Wang, W. Oehrl, S. M. Feller, and T.-H. Tan
Interaction of Hematopoietic Progenitor Kinase 1 with Adapter Proteins Crk and CrkL Leads to Synergistic Activation of c-Jun N-Terminal Kinase
Mol. Cell. Biol.,
February 1, 1999;
19(2):
1359 - 1368.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Ozaki, A. Oda, H. Wakao, J. Rhodes, B. J. Druker, A. Ishida, M. Wakui, S. Okamoto, K. Morita, M. Handa, et al.
Thrombopoietin Induces Association of Crkl With STAT5 But Not STAT3 in Human Platelets
Blood,
December 15, 1998;
92(12):
4652 - 4662.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Senechal, C. Heaney, B. Druker, and C. L. Sawyers
Structural Requirements for Function of the Crkl Adapter Protein in Fibroblasts and Hematopoietic Cells
Mol. Cell. Biol.,
September 1, 1998;
18(9):
5082 - 5090.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
A. P. Koval, M. Karas, Y. Zick, and D. LeRoith
Interplay of the Proto-oncogene Proteins CrkL and CrkII in Insulin-like Growth Factor-I Receptor-mediated Signal Transduction
J. Biol. Chem.,
June 12, 1998;
273(24):
14780 - 14787.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. de Jong, A. van Wijk, L. Haataja, N. Heisterkamp, and J. Groffen
BCR/ABL-induced Leukemogenesis Causes Phosphorylation of Hef1 and Its Association with Crkl
J. Biol. Chem.,
December 19, 1997;
272(51):
32649 - 32655.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Ahmad, Y. M. Alsayed, B. J. Druker, and L. C. Platanias
The Type I Interferon Receptor Mediates Tyrosine Phosphorylation of the CrkL Adaptor Protein
J. Biol. Chem.,
November 28, 1997;
272(48):
29991 - 29994.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. L. Barber, J. M. Mason, T. Fukazawa, K. A. Reedquist, B. J. Druker, H. Band, and A. D. D'Andrea
Erythropoietin and Interleukin-3 Activate Tyrosine Phosphorylation of CBL and Association With CRK Adaptor Proteins
Blood,
May 1, 1997;
89(9):
3166 - 3174.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X Zou, S Rudchenko, K Wong, and K Calame
Induction of c-myc transcription by the v-Abl tyrosine kinase requires Ras, Raf1, and cyclin-dependent kinases.
Genes & Dev.,
March 1, 1997;
11(5):
654 - 662.
[Abstract]
[PDF]
|
|
|
|
|
|
|
C. Heaney, K. Kolibaba, A. Bhat, T. Oda, S. Ohno, S. Fanning, and B. J. Druker
Direct Binding of CRKL to BCR-ABL Is Not Required for BCR-ABL Transformation
Blood,
January 1, 1997;
89(1):
297 - 306.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Salgia, E. Pisick, M. Sattler, J.-L. Li, N. Uemura, W.-K. Wong, S. A. Burky, H. Hirai, L. B. Chen, and J. D. Griffin
p130CAS Forms a Signaling Complex with the Adapter Protein CRKL in Hematopoietic Cells Transformed by the BCR/ABL Oncogene
J. Biol. Chem.,
October 11, 1996;
271(41):
25198 - 25203.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Senechal, J. Halpern, and C. L. Sawyers
The CRKL Adaptor Protein Transforms Fibroblasts and Functions in Transformation by the BCR-ABL Oncogene
J. Biol. Chem.,
September 20, 1996;
271(38):
23255 - 23261.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Maru, D. E. Afar, O. N. Witte, and M. Shibuya
The Dimerization Property of Glutathione S-Transferase Partially Reactivates Bcr-Abl Lacking the Oligomerization Domain
J. Biol. Chem.,
June 28, 1996;
271(26):
15353 - 15357.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Salgia, N. Uemura, K. Okuda, J.-L. Li, E. Pisick, M. Sattler, R. de Jong, B. Druker, N. Heisterkamp, L. B. Chen, et al.
CRKL Links p210[IMAGE] with Paxillin in Chronic Myelogenous Leukemia Cells
J. Biol. Chem.,
December 8, 1995;
270(49):
29145 - 29150.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y Shi, K Alin, and S P Goff
Abl-interactor-1, a novel SH3 protein binding to the carboxy-terminal portion of the Abl protein, suppresses v-abl transforming activity.
Genes & Dev.,
November 1, 1995;
9(21):
2583 - 2597.
[Abstract]
[PDF]
|
|
|
|
|
|
|
A. J. McGahon, W. K. Nishioka, S. J. Martin, A. Mahboubi, T. G. Cotter, and D. R. Green
Regulation of the Fas Apoptotic Cell Death Pathway by Abl
J. Biol. Chem.,
September 22, 1995;
270(38):
22625 - 22631.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. de Jong, J. t. Hoeve, N. Heisterkamp, and J. Groffen
Crkl Is Complexed with Tyrosine-phosphorylated Cbl in Ph-positive Leukemia
J. Biol. Chem.,
September 15, 1995;
270(37):
21468 - 21471.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Sattler, S. Verma, Y. B. Pride, R. Salgia, L. R. Rohrschneider, and J. D. Griffin
SHIP1, an SH2 Domain Containing Polyinositol-5-phosphatase, Regulates Migration through Two Critical Tyrosine Residues and Forms a Novel Signaling Complex with DOK1 and CRKL
J. Biol. Chem.,
January 19, 2001;
276(4):
2451 - 2458.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
