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| CYCLIC-AMP-INDUCED G1 PHASE ARREST MEDIATED BY AN INHIBITOR (P27(KIP1)) OF CYCLIN-DEPENDENT KINASE-4 ACTIVATION |
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| Author(s): KATO JY, MATSUOKA M, POLYAK K, MASSAGUE J, SHERR CJ |
| Source: CELL Volume: 79 Issue: 3 Pages: 487-496 Published: NOV 4 1994 |
| Times Cited: 664 References: 57 |
| Abstract: Cyclic AMP (cAMP) blocks the mitogenic effects of colony-stimulating factor 1 (CSF-1) in macrophages, inducing cell cycle arrest in mid-G1 phase. Complexes between cyclin D1 and cyclin-dependent kinase 4 (cdk4) assemble in growth arrested cells, but cdk4 is not phosphorylated in vivo by the cdk-activating kinase (CAK) and remains inactive. Although undetectable in lysates of cAMP-treated cells, active CAK is recovered after antibody precipitation, indicating that it is not the direct target of inhibition. Levels of the cdk inhibitor p27(Kip1) increase in cAMP-treated cells, and its immunodepletion from inhibitory lysates restores CAK-mediated cdk4 activation. Kip1 does not bind to CAK, but its association with cyclin D-cdk4 prevents CAK from phosphorylating and activating the holoenzyme. |
| Document Type: Article |
| Language: English |
Addresses:
1. ST JUDE CHILDRENS HOSP, HOWARD HUGHES MED INST, MEMPHIS, TN 38105 USA
2. ST JUDE CHILDRENS HOSP, TUMOR CELL BIOL LAB, MEMPHIS, TN 38105 USA
3. MEM SLOAN KETTERING CANC CTR, PROGRAM GENET & CELL BIOL, NEW YORK, NY 10021 USA |
| Publisher: CELL PRESS, 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: PQ488 |
| ISSN: 0092-8674 |
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