Specific inhibition of Elm1 kinase activity reveals functions required for early G1 events

被引:37
作者
Sreenivasan, A
Bishop, AC
Shokat, KM
Kellogg, DR [1 ]
机构
[1] Univ Calif Santa Cruz, Sinsheimer Labs, Dept Mol Cellular & Dev Biol, Santa Cruz, CA 95064 USA
[2] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA
关键词
D O I
10.1128/MCB.23.17.6327-6337.2003
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
In budding yeast, the Elm1 kinase is required for coordination of cell growth and cell division at G(2)/M. Elm1 is also required for efficient cytokinesis and for regulation of Swe1, the budding yeast homolog of the Wee1 kinase. To further characterize Elm1 function, we engineered an ELM1 allele that can be rapidly and selectively inhibited in vivo. We found that inhibition of Elm1 kinase activity during G(2) results in a phenotype similar to the phenotype caused by deletion of the ELM1 gene, as expected. However, inhibition of Elm1 kinase activity earlier in the cell cycle results in a prolonged G(1) delay. The G(1) requirement for Elm1 kinase activity occurs before bud emergence, polarization of the septins, and synthesis of G(1) cyclins. Inhibition of Elm1 kinase activity during early G(1) also causes defects in the organization of septins, and inhibition of Elm1 kinase activity in a strain lacking the redundant G(1) cyclins CLN1 and CLN2 is lethal. These results demonstrate that the Elm1 kinase plays an important role in G(1) events required for bud emergence and septin organization.
引用
收藏
页码:6327 / 6337
页数:11
相关论文
共 48 条
[1]   Control of mitotic events by Nap1 and the Gin4 kinase [J].
Altman, R ;
Kellogg, D .
JOURNAL OF CELL BIOLOGY, 1997, 138 (01) :119-130
[2]   Nim1-related kinases coordinate cell cycle progression with the organization of the peripheral cytoskeleton in yeast [J].
Barral, Y ;
Parra, M ;
Bidlingmaier, S ;
Snyder, M .
GENES & DEVELOPMENT, 1999, 13 (02) :176-187
[3]   GENETIC-ANALYSIS OF CLN CDC28 REGULATION OF CELL MORPHOGENESIS IN BUDDING YEAST [J].
BENTON, BK ;
TINKELENBERG, AH ;
JEAN, D ;
PLUMP, SD ;
CROSS, FR .
EMBO JOURNAL, 1993, 12 (13) :5267-5275
[4]   Unnatural ligands for engineered proteins: New tools for chemical genetics [J].
Bishop, A ;
Buzko, O ;
Heyeck-Dumas, S ;
Jung, I ;
Kraybill, B ;
Liu, Y ;
Shah, K ;
Ulrich, S ;
Witucki, L ;
Yang, F ;
Zhang, C ;
Shokat, KM .
ANNUAL REVIEW OF BIOPHYSICS AND BIOMOLECULAR STRUCTURE, 2000, 29 :577-606
[5]   A chemical switch for inhibitor-sensitive alleles of any protein kinase [J].
Bishop, AC ;
Ubersax, JA ;
Petsch, DT ;
Matheos, DP ;
Gray, NS ;
Blethrow, J ;
Shimizu, E ;
Tsien, JZ ;
Schultz, PG ;
Rose, MD ;
Wood, JL ;
Morgan, DO ;
Shokat, KM .
NATURE, 2000, 407 (6802) :395-401
[6]   Design of allele-specific inhibitors to probe protein kinase signaling [J].
Bishop, AC ;
Shah, K ;
Liu, Y ;
Witucki, L ;
Kung, CY ;
Shokat, KM .
CURRENT BIOLOGY, 1998, 8 (05) :257-266
[7]   Generation of monospecific nanomolar tyrosine kinase inhibitors via a chemical genetic approach [J].
Bishop, AC ;
Kung, CY ;
Shah, K ;
Witucki, L ;
Shokat, KM ;
Liu, Y .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1999, 121 (04) :627-631
[8]   REGULATION OF DIMORPHISM IN SACCHAROMYCES-CEREVISIAE - INVOLVEMENT OF THE NOVEL PROTEIN-KINASE HOMOLOG ELM1P AND PROTEIN PHOSPHATASE 2A [J].
BLACKETER, MJ ;
KOEHLER, CM ;
COATS, SG ;
MYERS, AM ;
MADAULE, P .
MOLECULAR AND CELLULAR BIOLOGY, 1993, 13 (09) :5567-5581
[9]  
Bouquin N, 2000, J CELL SCI, V113, P1435
[10]   The septins are required for the mitosis-specific activation of the Gin4 kinase [J].
Carroll, CW ;
Altman, R ;
Schieltz, D ;
Yates, JR ;
Kellogg, D .
JOURNAL OF CELL BIOLOGY, 1998, 143 (03) :709-717