Cyclic AMP-induced G1 phase arrest mediated by an inhibitor (p27(Kip1)) of cyclin-dependent kinase 4 activation Journal Article

  

Authors:	Kato, J. Y.; Matsuoka, M.; Polyak, K.; Massague, J.; Sherr, C. J.
Article Title:	Cyclic AMP-induced G1 phase arrest mediated by an inhibitor (p27(Kip1)) of cyclin-dependent kinase 4 activation
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 p27Kip1 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. © 1994.
Keywords:	controlled study; nonhuman; comparative study; flow cytometry; animal cell; mouse; animal; mice; cells, cultured; enzyme inhibition; enzyme activation; enzyme activity; phosphorylation; time factors; animalia; dna; protein-serine-threonine kinases; prostaglandin e2; cyclic amp; cycline; macrophage; macrophages; phosphotransferase; rapamycin; antibody; sirolimus; cell cycle g1 phase; g1 phase; autoradiography; colony stimulating factor 1; peptide mapping; fungal proteins; microtubule-associated proteins; forskolin; dna content; antigen-antibody complex; precipitin tests; isobutylmethylxanthine; priority journal; article; cyclic amp derivative; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; aphidicolin; polyenes
Journal Title:	Cell
Volume:	79
Issue:	3
ISSN:	0092-8674
Publisher:	Cell Press
Date Published:	1994-11-04
Start Page:	487
End Page:	496
Language:	English
DOI:	10.1016/0092-8674(94)90257-7
PROVIDER:	scopus
PUBMED:	7954814
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0027973043&doi=10.1016%2f0092-8674%2894%2990257-7&partnerID=40&md5=ee8eefae50e0b6bcac46d31cd7669cd9
Notes:	Export Date: 14 January 2019 -- Article -- -- Source: Scopus

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