Cdk1 coordinates cell-surface growth with the cell cycle.
The mechanisms that control cell growth during the cell cycle are poorly understood. In budding yeast, cyclin dependent kinase 1 (Cdk1) triggers polarization of the actin cytoskeleton and bud emergence in late G1 through activation of the Cdc42 GTPase. However, Cdk1 is not thought to be required for subsequent growth of the bud. Here, we show that Cdk1 has an unexpected role in controlling bud growth after bud emergence. Moreover, we show that G1 cyclin-Cdk1 complexes specifically phosphorylate multiple proteins associated with Cdc24, the guanine nucleotide-exchange factor (GEF) that activates the Cdc42 GTPase. A mutant form of a Cdc24-associated protein that fails to undergo Cdk1-dependent phosphorylation causes defects in bud growth. These results provide a direct link between Cdk1 activity and the control of polarized cell growth.
McCusker
Derek
D
Department of Molecular, Cell and Developmental Biology, University of California, 1156 High Street, Santa Cruz, CA 95064, USA.
Denison
Carilee
C
Anderson
Scott
S
Egelhofer
Thea A
TA
Yates
John R
JR
Gygi
Steven P
SP
Kellogg
Douglas R
DR
D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D016764:Cell Polarity / Q000187:drug effects; D056746:Cyclin G; D016213:Cyclins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005089:Exocytosis; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D007716:Kluyveromyces / Q000254:growth & development; D046912:Multiprotein Complexes / Q000378:metabolism; D009154:Mutation; D010766:Phosphorylation; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D004718:Saccharomycetales / Q000187:drug effects / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism; D013997:Time Factors; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*
C479693:1-tert-butyl-3-naphthalen-1-ylmethyl-1H-pyrazolo(3,4-d)pyrimidin-4-ylemine; D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D056746:Cyclin G; D016213:Cyclins; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D020662:Guanine Nucleotide Exchange Factors; D046912:Multiprotein Complexes; D011720:Pyrazoles; D011743:Pyrimidines; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D016203:CDC2 Protein Kinase; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D020764:cdc42 GTP-Binding Protein