|
Originally published In Press as doi:10.1074/jbc.M301523200 on June 12, 2003
J. Biol. Chem., Vol. 278, Issue 35, 32544-32551, August 29, 2003
Activation of Protein Kinase C by All-trans-retinoic Acid*
Suman Kambhampati  ,
Yongzhong Li ,
Amit Verma ,
Antonella Sassano ,
Beata Majchrzak  ,
Dilip K. Deb ¶,
Simrit Parmar ,
Nick Giafis ,
Dhananjaya V. Kalvakolanu ||,
Arshad Rahman **,
Shahab Uddin ,
Saverio Minucci ,
Martin S. Tallman ,
Eleanor N. Fish and
Leonidas C. Platanias ¶¶
From the
Robert H. Lurie Comprehensive Cancer
Center and the Division of Hematology-Oncology, Northwestern University
Feinberg School of Medicine and Lakeside Veterans Affairs Medical Center,
Chicago, Illinois 60611, the Division of Cell
and Molecular Biology, Toronto Research Institute, University Health Network,
and the Department of Immunology, University of Toronto, Toronto, Ontario M5G
2M1, Canada, the **Department of Pediatrics,
University of Rochester School of Medicine, Rochester, New York 14642, the
¶Ben May Cancer Institute and the
Section of Hematology-Oncology,
University of Chicago, Chicago, Illinois 60637, the
||Department of Microbiology and Immunology,
University of Maryland School of Medicine, Baltimore, Maryland 21201, and the
Department of Experimental Oncology,
European Institute of Oncology, Milan 20141, Italy
All-trans-retinoic acid (RA) is a potent inhibitor of leukemia
cell proliferation and induces differentiation of acute promyelocytic leukemia
cells in vitro and in vivo. For RA to induce its biological
effects in target cells, binding to specific retinoic acid nuclear receptors
is required. The resulting complexes bind to RA-responsive elements (RAREs) in
the promoters of RA-inducible genes to initiate gene transcription and to
generate protein products that mediate the biological effects of RA. In this
report, we provide evidence that a member of the protein kinase C (PKC) family
of proteins, PKC , is activated during RA treatment of the NB-4 and
HL-60 acute myeloid leukemia cell lines as well as the MCF-7 breast cancer
cell line. Such RA-dependent phosphorylation was also observed in primary
acute promyelocytic leukemia cells and resulted in activation of the kinase
domain of PKC. In studies aimed at understanding the functional
relevance of PKC in the induction of RA responses, we found that
pharmacological inhibition of PKC (but not of other PKC isoforms)
diminished RA-dependent gene transcription via RAREs. On the other hand,
overexpression of a constitutively active form of the kinase strongly enhanced
RA-dependent gene transcription via RAREs. Gel shift assays and chromatin
immunoprecipitation studies demonstrated that PKC associated with
retinoic acid receptor- and was present in an RA-inducible protein
complex that bound to RAREs. Pharmacological inhibition of PKC activity
abrogated the induction of cell differentiation and growth inhibition of NB-4
blast cells, demonstrating that its function is required for such effects.
Altogether, our data provide strong evidence that PKC is activated in
an RA-dependent manner and plays a critical role in the generation of the
biological effects of RA in malignant cells.
Received for publication, February 12, 2003
, and in revised form, May 12, 2003.
* This work was supported by a merit review grant from the Department of
Veterans Affairs and National Institutes of Health Grants CA77816 and CA94079
(to L. C. P.) and by Canadian Institutes of Health Research Grant MOP15094
(to E. N. F.). S. K. is a recipient of a fellowship award from the
Lauri Straus Leukemia Foundation. A. V. is a recipient of an ASCO Young
Investigator Award. The costs of publication of this article were defrayed in
part by the payment of page charges. This article must therefore be hereby
marked "advertisement" in accordance with 18 U.S.C.
Section 1734 solely to indicate this fact.
¶¶
To whom correspondence should be addressed: Robert H. Lurie Comprehensive
Cancer Center, Northwestern University Medical School, 710 North Fairbanks
Ave., Olson Pavilion 8250, Chicago, IL 60611. Tel.: 312-503-4267; Fax:
312-908-1372; E-mail:
l-platanias{at}northwestern.edu.
 CiteULike  Complore  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
T. Kogai, E. Ohashi, M. S. Jacobs, S. Sajid-Crockett, M. L. Fisher, Y. Kanamoto, and G. A. Brent
Retinoic Acid Stimulation of the Sodium/Iodide Symporter in MCF-7 Breast Cancer Cells Is Meditated by the Insulin Growth Factor-I/Phosphatidylinositol 3-Kinase and p38 Mitogen-Activated Protein Kinase Signaling Pathways
J. Clin. Endocrinol. Metab.,
May 1, 2008;
93(5):
1884 - 1892.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Alzamora, L. R. Brown, and B. J. Harvey
Direct Binding and Activation of Protein Kinase C Isoforms by Aldosterone and 17{beta}-Estradiol
Mol. Endocrinol.,
November 1, 2007;
21(11):
2637 - 2650.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Masia, S. Alvarez, A. R. de Lera, and D. Barettino
Rapid, Nongenomic Actions of Retinoic Acid on Phosphatidylinositol-3-Kinase Signaling Pathway Mediated by the Retinoic Acid Receptor
Mol. Endocrinol.,
October 1, 2007;
21(10):
2391 - 2402.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Rizzi, M. P. Tschan, C. Britschgi, A. Britschgi, B. Hugli, T. J. Grob, N. Leupin, B. U. Mueller, H.-U. Simon, A. Ziemiecki, et al.
The death-associated protein kinase 2 is up-regulated during normal myeloid differentiation and enhances neutrophil maturation in myeloid leukemic cells
J. Leukoc. Biol.,
June 1, 2007;
81(6):
1599 - 1608.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Sassano, E. Katsoulidis, G. Antico, J. K. Altman, A. J. Redig, S. Minucci, M. S. Tallman, and L. C. Platanias
Suppressive Effects of Statins on Acute Promyelocytic Leukemia Cells
Cancer Res.,
May 1, 2007;
67(9):
4524 - 4532.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Chen, M. Dokmanovic, W. D. Stein, R. J. Ardecky, and I. B. Roninson
Agonist and Antagonist of Retinoic Acid Receptors Cause Similar Changes in Gene Expression and Induce Senescence-like Growth Arrest in MCF-7 Breast Carcinoma Cells.
Cancer Res.,
September 1, 2006;
66(17):
8749 - 8761.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Aggarwal, S.-W. Kim, K. Cheon, F. H. Tabassam, J.-H. Yoon, and J. S. Koo
Nonclassical Action of Retinoic Acid on the Activation of the cAMP Response Element-binding Protein in Normal Human Bronchial Epithelial Cells
Mol. Biol. Cell,
February 1, 2006;
17(2):
566 - 575.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K.-W. Zhao, D. Li, Q. Zhao, Y. Huang, R. H. Silverman, P. J. Sims, and G.-Q. Chen
Interferon-{alpha}-induced Expression of Phospholipid Scramblase 1 through STAT1 Requires the Sequential Activation of Protein Kinase C{delta} and JNK
J. Biol. Chem.,
December 30, 2005;
280(52):
42707 - 42714.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Chaudhuri, S. M. Colles, P. L. Fox, and L. M. Graham
Protein Kinase C{delta}-Dependent Phosphorylation of Syndecan-4 Regulates Cell Migration
Circ. Res.,
September 30, 2005;
97(7):
674 - 681.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Hampson, H. Chahal, F. Khanim, R. Hayden, A. Mulder, L. K. Assi, C. M. Bunce, and J. M. Lord
PEP005, a selective small-molecule activator of protein kinase C, has potent antileukemic activity mediated via the delta isoform of PKC
Blood,
August 15, 2005;
106(4):
1362 - 1368.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. B. Barry and V. Giguere
Epidermal Growth Factor-Induced Signaling in Breast Cancer Cells Results in Selective Target Gene Activation by Orphan Nuclear Receptor Estrogen-Related Receptor {alpha}
Cancer Res.,
July 15, 2005;
65(14):
6120 - 6129.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Murugappan, H. Shankar, S. Bhamidipati, R. T. Dorsam, J. Jin, and S. P. Kunapuli
Molecular mechanism and functional implications of thrombin-mediated tyrosine phosphorylation of PKC{delta} in platelets
Blood,
July 15, 2005;
106(2):
550 - 557.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Tanmahasamut and N. Sidell
Up-Regulation of Gap Junctional Intercellular Communication and Connexin43 Expression by Retinoic Acid in Human Endometrial Stromal Cells
J. Clin. Endocrinol. Metab.,
July 1, 2005;
90(7):
4151 - 4156.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Li, S. Batra, A. Sassano, B. Majchrzak, D. E. Levy, M. Gaestel, E. N. Fish, R. J. Davis, and L. C. Platanias
Activation of Mitogen-activated Protein Kinase Kinase (MKK) 3 and MKK6 by Type I Interferons
J. Biol. Chem.,
March 18, 2005;
280(11):
10001 - 10010.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Lal, Y. Li, J. Smith, A. Sassano, S. Uddin, S. Parmar, M. S. Tallman, S. Minucci, N. Hay, and L. C. Platanias
Activation of the p70 S6 kinase by all-trans-retinoic acid in acute promyelocytic leukemia cells
Blood,
February 15, 2005;
105(4):
1669 - 1677.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K.-W. Zhao, X. Li, Q. Zhao, Y. Huang, D. Li, Z.-G. Peng, W.-Z. Shen, J. Zhao, Q. Zhou, Z. Chen, et al.
Protein kinase C{delta} mediates retinoic acid and phorbol myristate acetate-induced phospholipid scramblase 1 gene expression: its role in leukemic cell differentiation
Blood,
December 1, 2004;
104(12):
3731 - 3738.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. N. JACKSON and D. A. FOSTER
The enigmatic protein kinase C{delta}: complex roles in cell proliferation and survival
FASEB J,
April 1, 2004;
18(6):
627 - 636.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Murugappan, F. Tuluc, R. T. Dorsam, H. Shankar, and S. P. Kunapuli
Differential Role of Protein Kinase C{delta} Isoform in Agonist-induced Dense Granule Secretion in Human Platelets
J. Biol. Chem.,
January 23, 2004;
279(4):
2360 - 2367.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Li, A. Sassano, B. Majchrzak, D. K. Deb, D. E. Levy, M. Gaestel, A. R. Nebreda, E. N. Fish, and L. C. Platanias
Role of p38{alpha} Map Kinase in Type I Interferon Signaling
J. Biol. Chem.,
January 9, 2004;
279(2):
970 - 979.
[Abstract]
[Full Text]
[PDF]
|
|
|
Copyright © 2003 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|
