CYCLIC-AMP-INDUCED G1 PHASE ARREST MEDIATED BY AN INHIBITOR (P27(KIP1)) OF CYCLIN-DEPENDENT KINASE-4 ACTIVATION

被引：737

作者：

KATO, JY

MATSUOKA, M

POLYAK, K

MASSAGUE, J

SHERR, CJ

机构：

[1] ST JUDE CHILDRENS RES HOSP, HOWARD HUGHES MED INST, MEMPHIS, TN 38105 USA

[2] ST JUDE CHILDRENS RES HOSP, TUMOR CELL BIOL LAB, MEMPHIS, TN 38105 USA

[3] MEM SLOAN KETTERING CANC CTR, PROGRAM GENET & CELL BIOL, NEW YORK, NY 10021 USA

来源：

CELL | 1994年 / 79卷 / 03期

关键词：

D O I：

10.1016/0092-8674(94)90257-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：487 / 496

页数：10

共 57 条

[11] CDK2 ENCODES A 33-KDA CYCLIN-A-ASSOCIATED PROTEIN-KINASE AND IS EXPRESSED BEFORE CDC2 IN THE CELL-CYCLE [J].