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Science 26 January 1996:
Vol. 271. no. 5248, pp. 499 - 502
DOI: 10.1126/science.271.5248.499
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Reports

Dependence of Cyclin E-CDK2 Kinase Activity on Cell Anchorage

Fang Fang (1) (2),  Gertraud Orend (1),  Nobumoto Watanabe,  Tony Hunter,  Erkki Ruoslahti (3)

Most nonmalignant cells are anchorage-dependent; they require substrate attachment for growth and, in some instances, survival. This requirement is lost on oncogenic transformation. The cyclin E-CDK2 complex, which is required for the G1-S transition of the cell cycle, was activated in late G1 phase in attached human fibroblasts, but not in fibroblasts maintained in suspension. In transformed fibroblasts the complex was active regardless of attachment. The lack of cyclin E-CDK2 activity in suspended cells appeared to result from increased expression of CDK2 inhibitors and a concomitant decrease in phosphorylation of CDK2 on threonine-160. Suppression of cyclin E-CDK2 activity may thus underlie the anchorage dependence of cell growth.


F. Fang, G. Orend, E. Ruoslahti, La Jolla Cancer Research Foundation, Cancer Center, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
N. Watanabe and T. Hunter, Molecular Biology and Virology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
(1) These authors contributed equally to this work.
(2) Present address: Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
(3) To whom correspondence should be addressed.


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Role of Tyrosine Kinases in Extracellular Matrix–Mediated Modulation of Arterial Smooth Muscle Cell Phenotype.
U. Hedin, J. Thyberg, J. Roy, A. Dumitrescu, and P. K. Tran (1997)
Arterioscler Thromb Vasc Biol 17, 1977-1984
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Retinoblastoma Protein-dependent Growth Signal Conflict and Caspase Activity Are Required for Protein Kinase C-signaled Apoptosis of Prostate Epithelial Cells.
X. Zhao, J. E. Gschwend, C. T. Powell, R. G. Foster, K. C. Day, and M. L. Day (1997)
J. Biol. Chem. 272, 22751-22757
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Cyclin E-CDK2 is a regulator of p27Kip1..
R J Sheaff, M Groudine, M Gordon, J M Roberts, and B E Clurman (1997)
Genes & Dev. 11, 1464-1478
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Overexpression of the Integrin-linked Kinase Promotes Anchorage-independent Cell Cycle Progression.
G. Radeva, T. Petrocelli, E. Behrend, C. Leung-Hagesteijn, J. Filmus, J. Slingerland, and S. Dedhar (1997)
J. Biol. Chem. 272, 13937-13944
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Focal Adhesion Kinase Overexpression Enhances Ras-dependent Integrin Signaling to ERK2/Mitogen-activated Protein Kinase through Interactions with and Activation of c-Src.
D. D. Schlaepfer and T. Hunter (1997)
J. Biol. Chem. 272, 13189-13195
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Cell Anchorage Permits Efficient Signal Transduction Between Ras and Its Downstream Kinases.
T. H. Lin, Q. Chen, A. Howe, and R. L. Juliano (1997)
J. Biol. Chem. 272, 8849-8852
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Cell Anchorage Regulates Apoptosis through the Retinoblastoma Tumor Suppressor/E2F Pathway.
M. L. Day, R. G. Foster, K. C. Day, X. Zhao, P. Humphrey, P. Swanson, A. A. Postigo, S. H. Zhang, and D. C. Dean (1997)
J. Biol. Chem. 272, 8125-8128
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Integrin-mediated Activation of MAP Kinase Is Independent of FAK: Evidence for Dual Integrin Signaling Pathways in Fibroblasts.
T. H. Lin, A. E. Aplin, Y. Shen, Q. Chen, M. Schaller, L. Romer, I. Aukhil, and R.L. Juliano (1997)
J. Cell Biol. 136, 1385-1395
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Cooperating oncogenes converge to regulate cyclin/cdk complexes..
A C Lloyd, F Obermuller, S Staddon, C F Barth, M McMahon, and H Land (1997)
Genes & Dev. 11, 663-677
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The subcellular locations of p15(Ink4b) and p27(Kip1) coordinate their inhibitory interactions with cdk4 and cdk2..
I Reynisdottir and J Massague (1997)
Genes & Dev. 11, 492-503
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Extracellular ATP Induces Anchorage-independent Expression of Cyclin A and Rescues the Transformed Phenotype of a Ras-resistant Mutant Cell Line.
J.-J. Yang and R. S. Krauss (1997)
J. Biol. Chem. 272, 3103-3108
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Anchorage-dependent Cell Cycle Progression.
R. K. Assoian (1997)
J. Cell Biol. 136, 1-4
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Integrin regulation of c-Abl tyrosine kinase activity and cytoplasmic-nuclear transport.
J. M. Lewis, R. Baskaran, S. Taagepera, M. A. Schwartz, and J. Y. J. Wang (1996)
PNAS 93, 15174-15179
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Decorin-induced Growth Suppression Is Associated with Up-regulation of p21, an Inhibitor of Cyclin-dependent Kinases.
A. De Luca, M. Santra, A. Baldi, A. Giordano, and R. V. Iozzo (1996)
J. Biol. Chem. 271, 18961-18965
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alpha 1-Proteinase Inhibitor, alpha 1-Antichymotrypsin, and alpha 2-Macroglobulin Are the Antiapoptotic Factors of Vascular Smooth Muscle Cells.
Y. Ikari, E. Mulvihill, and S. M. Schwartz (2001)
J. Biol. Chem. 276, 11798-11803
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