|
|
|
|||||||
|
|||||||||
J Biol Chem, Vol. 275, Issue 9, 6267-6275, March 3, 2000
From the Department of Molecular and Experimental Medicine, The
Scripps Research Institute, BCC239, La Jolla, California 92037
The retroviral oncogene p3k
(v-p3k) of avian sarcoma virus 16 (ASV16) codes for the
catalytic subunit of phosphoinositide (PI) 3-kinase, p110
The Catalytic Subunit of Phosphoinositide 3-Kinase: Requirements
for Oncogenicity*
,
. The v-P3k
protein is oncogenic in vivo and in vitro; its
cellular counterpart, c-P3k, lacks oncogenicity. Fusion of viral Gag
sequences to the amino terminus of c-P3k activates the transforming
potential. Activation can also be achieved by the addition of a
myristylation signal to the amino terminus or of a farnesylation signal
to the carboxyl terminus of c-P3k. A mutated myristylation signal was
equally effective; it also caused a strong increase in the kinase
activity of P3k. Mutations that inactivate lipid kinase activity
abolish oncogenicity. The transforming activity of P3k is correlated
with the ability to induce activating phosphorylation in Akt. Point
mutations and amino-terminal deletions recorded in v-P3k were shown to
be irrelevant to the activation of oncogenic potential. Interactions of
P3k with the regulatory subunit of PI 3-kinase, p85, or with Ras are
not required for transformation. These results support the conclusion
that the oncogenicity of P3k depends on constitutive lipid kinase
activity. Akt is an important and probably essential downstream
component of the oncogenic signal from P3k.
*
This work was supported by National Institutes of Health
Grants CA 42564 and CA 78230. Oligonucleotides were synthesized by the
Department of Molecular and Experimental Medicine Service Laboratory
supported by The Sam and Rose Stein Endowment Fund.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Current address: Institute of Genetics, University of Salzburg,
5020 Salzburg, Austria.
§
Current address: Digital Gene Technology, 11149 North Torrey Pines
Rd., La Jolla, CA 92037.
¶
To whom correspondence should be addressed. Tel.:
858-784-9728; Fax: 858-784-2070; E-mail: pkvogt@scripps.edu.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Denley, M. Gymnopoulos, S. Kang, C. Mitchell, and P. K. Vogt Requirement of Phosphatidylinositol(3,4,5)Trisphosphate in Phosphatidylinositol 3-Kinase-Induced Oncogenic Transformation Mol. Cancer Res., July 1, 2009; 7(7): 1132 - 1138. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Kakinuma, B. C. Roy, Y. Zhu, Y. Wang, and R. Kiyama Kank regulates RhoA-dependent formation of actin stress fibers and cell migration via 14-3-3 in PI3K-Akt signaling J. Cell Biol., October 14, 2008; 181(3): 537 - 549. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Zhao and P. K. Vogt Helical domain and kinase domain mutations in p110{alpha} of phosphatidylinositol 3-kinase induce gain of function by different mechanisms PNAS, February 19, 2008; 105(7): 2652 - 2657. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Kawamata, J. Chen, and H. P. Koeffler Suberoylanilide hydroxamic acid (SAHA; vorinostat) suppresses translation of cyclin D1 in mantle cell lymphoma cells Blood, October 1, 2007; 110(7): 2667 - 2673. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Renner, J. Fominaya, S. Alonso, C. Blanco-Aparicio, J. F.M. Leal, and A. Carnero Mst1, RanBP2 and eIF4G are new markers for in vivo PI3K activation in murine and human prostate Carcinogenesis, July 1, 2007; 28(7): 1418 - 1425. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gymnopoulos, M.-A. Elsliger, and P. K. Vogt Rare cancer-specific mutations in PIK3CA show gain of function PNAS, March 27, 2007; 104(13): 5569 - 5574. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-i. Yaguchi, Y. Fukui, I. Koshimizu, H. Yoshimi, T. Matsuno, H. Gouda, S. Hirono, K. Yamazaki, and T. Yamori Antitumor activity of ZSTK474, a new phosphatidylinositol 3-kinase inhibitor. J Natl Cancer Inst, April 19, 2006; 98(8): 545 - 556. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Ding, J. Li, J. Chen, H. Chen, W. Ouyang, R. Zhang, C. Xue, D. Zhang, S. Amin, D. Desai, et al. Effects of Polycyclic Aromatic Hydrocarbons (PAHs) on Vascular Endothelial Growth Factor Induction through Phosphatidylinositol 3-Kinase/AP-1-dependent, HIF-1{alpha}-independent Pathway J. Biol. Chem., April 7, 2006; 281(14): 9093 - 9100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kang, A. Denley, B. Vanhaesebroeck, and P. K. Vogt Oncogenic transformation induced by the p110beta, -{gamma}, and -{delta} isoforms of class I phosphoinositide 3-kinase PNAS, January 31, 2006; 103(5): 1289 - 1294. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. Bader, S. Kang, and P. K. Vogt Cancer-specific mutations in PIK3CA are oncogenic in vivo PNAS, January 31, 2006; 103(5): 1475 - 1479. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. Bader and P. K. Vogt Inhibition of Protein Synthesis by Y Box-Binding Protein 1 Blocks Oncogenic Cell Transformation Mol. Cell. Biol., March 15, 2005; 25(6): 2095 - 2106. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kang, A. G. Bader, and P. K. Vogt Phosphatidylinositol 3-kinase mutations identified in human cancer are oncogenic PNAS, January 18, 2005; 102(3): 802 - 807. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Aoki, H. Jiang, and P. K. Vogt Proteasomal degradation of the FoxO1 transcriptional regulator in cells transformed by the P3k and Akt oncoproteins PNAS, September 14, 2004; 101(37): 13613 - 13617. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Joosten, M. Blazquez-Domingo, F. Lindeboom, F. Boulme, A. Van Hoven-Beijen, B. Habermann, B. Lowenberg, H. Beug, E. W. Mullner, R. Delwel, et al. Translational Control of Putative Protooncogene Nm23-M2 by Cytokines via Phosphoinositide 3-Kinase Signaling J. Biol. Chem., September 10, 2004; 279(37): 38169 - 38176. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Li, G. Davidson, Y. Huang, B.-H. Jiang, X. Shi, M. Costa, and C. Huang Nickel Compounds Act through Phosphatidylinositol-3-kinase/Akt-Dependent, p70S6k-Independent Pathway to Induce Hypoxia Inducible Factor Transactivation and Cap43 Expression in Mouse Epidermal Cl41 Cells Cancer Res., January 1, 2004; 64(1): 94 - 101. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. Bader, K. A. Felts, N. Jiang, H. W. Chang, and P. K. Vogt Y box-binding protein 1 induces resistance to oncogenic transformation by the phosphatidylinositol 3-kinase pathway PNAS, October 14, 2003; 100(21): 12384 - 12389. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Sawyer, J. Sturge, D. C. Bennett, M. J. O'Hare, W. E. Allen, J. Bain, G. E. Jones, and B. Vanhaesebroeck Regulation of Breast Cancer Cell Chemotaxis by the Phosphoinositide 3-Kinase p110{delta} Cancer Res., April 1, 2003; 63(7): 1667 - 1675. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Ringshausen, F. Schneller, C. Bogner, S. Hipp, J. Duyster, C. Peschel, and T. Decker Constitutively activated phosphatidylinositol-3 kinase (PI-3K) is involved in the defect of apoptosis in B-CLL: association with protein kinase Cdelta Blood, November 15, 2002; 100(10): 3741 - 3748. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. A. Millot, W. Vainchenker, D. Dumenil, and F. Svinarchuk Distinct effects of thrombopoietin depending on a threshold level of activated Mpl in BaF-3 cells J. Cell Sci., January 6, 2002; 115(11): 2329 - 2337. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. H. Hsu, A. C. Lochan, and D. S. Cowen Activation of Akt1 by Human 5-Hydroxytryptamine (Serotonin)1B Receptors Is Sensitive to Inhibitors of MEK J. Pharmacol. Exp. Ther., August 1, 2001; 298(2): 825 - 832. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B.-H. Jiang, G. Jiang, J. Z. Zheng, Z. Lu, T. Hunter, and P. K. Vogt Phosphatidylinositol 3-Kinase Signaling Controls Levels of Hypoxia-inducible Factor 1 Cell Growth Differ., July 1, 2001; 12(7): 363 - 369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Aoki, E. Blazek, and P. K. Vogt A role of the kinase mTOR in cellular transformation induced by the oncoproteins P3k and Akt PNAS, December 22, 2000; (2000) 11528498. [Abstract] [Full Text]
|
|
|
|
|
|
T. Akagi, T. Shishido, K. Murata, and H. Hanafusa v-Crk activates the phosphoinositide 3-kinase/AKT pathway in transformation PNAS, June 13, 2000; (2000) 140210297. [Abstract] [Full Text]
|
|
|
|
|
|
B. Belletti, M. Prisco, A. Morrione, B. Valentinis, M. Navarro, and R. Baserga Regulation of Id2 Gene Expression by the Insulin-like Growth Factor I Receptor Requires Signaling by Phosphatidylinositol 3-Kinase J. Biol. Chem., April 20, 2001; 276(17): 13867 - 13874. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Aoki, E. Blazek, and P. K. Vogt A role of the kinase mTOR in cellular transformation induced by the oncoproteins P3k and Akt PNAS, January 2, 2001; 98(1): 136 - 141. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Akagi, T. Shishido, K. Murata, and H. Hanafusa v-Crk activates the phosphoinositide 3-kinase/AKT pathway in transformation PNAS, June 20, 2000; 97(13): 7290 - 7295. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |