Sinsheimer Laboratories, Department of Molecular, Cellular and Developmental Biology, University of California, Santa Cruz, CA 95064, USA
(e-mail: kellogg{at}darwin.ucsc.edu)
![]() |
Summary |
---|
Key words: Wee1, Swe1, Cell growth, Cell division, Mitosis, Yeast
![]() |
Introduction |
---|
![]() |
Wee1-related kinases delay entry into mitosis and are required for cell-size control in yeasts |
---|
|
Recent work has shown that Swe1, the budding yeast homolog of Wee1, also delays entry into mitosis and is required for cell-size control (Harvey and Kellogg, 2003; Jorgensen et al., 2002
). swe1
cells undergo premature entry into mitosis before sufficient growth of the daughter bud has occurred, producing abnormally small cells (Fig. 1B) (Harvey and Kellogg, 2003
). In addition, loss of function of Mih1, the budding yeast homolog of Cdc25, causes delayed entry into mitosis and produces abnormally large cells (Harvey and Kellogg, 2003
; Russell et al., 1989
) (G. Pal and D.K., unpublished). Finally, budding yeast Swe1 can rescue a temperature-sensitive wee1- mutant in fission yeast (Booher et al., 1993
). These observations demonstrate that the basic functions of fission yeast Wee1 and Cdc25 have been conserved in budding yeast. Loss of function of Wee1-related kinases in Xenopus and Drosophila also causes premature entry into mitosis; however, a requirement for Wee1 in cell-size control has not yet been demonstrated in animal cells (Walter et al., 2000
) (S. Campbell, personal communication).
A requirement for Swe1 in coordination of budding yeast growth and division was missed in early studies because the cell-size phenotype of swe1 mutants is more subtle than that of fission yeast wee1- mutants: a smaller proportion of swe1
cells show a cell-size phenotype (Harvey and Kellogg, 2003
). This is probably owing to different growth and division strategies used by fission yeast and budding yeast. Fission yeast grow at their ends and undergo medial division to produce two daughter cells of equal size. Premature entry into mitosis therefore leads to birth of two equally sized daughter cells that are smaller than normal (Fig. 1A). Budding yeast grow by formation of a daughter bud, and all cell growth occurs in the daughter bud after G1 phase. swe1
cells enter mitosis prematurely before the daughter bud has finished growing, and cytokinesis therefore yields a mother cell of normal size and an abnormally small daughter cell (Fig. 1B) (Harvey and Kellogg, 2003
). Mother cells are of a normal size because the G1 cell-size checkpoint delays cells in G1 until they have reached a critical cell size (Fig. 2) (Hartwell and Unger, 1977
; Harvey and Kellogg, 2003
; Johnston et al., 1977
; Rupes, 2002
). Furthermore, once a mother cell reaches this critical size, it can bud repeatedly to produce daughter cells. A population of swe1
cells should therefore be composed of mother cells that are of a normal size and newly born daughter cells that are abnormally small. Another difference between fission yeast and budding yeast is that wee1- mutants are unviable at elevated temperatures, whereas swe1
mutants are viable. This might be due to the existence of redundant mechanisms in budding yeast that can partially compensate for a loss of Swe1 function.
|
![]() |
Physiological roles of Wee1-related kinases |
---|
More recent experiments in both budding yeast and fission yeast provide further support for the idea that Wee1-related kinases play a direct role in coordinating growth and division at the G2/M transition. These experiments found that depolymerization of the actin cytoskeleton with latrunculin A causes a G2/M delay that is dependent upon tyrosine phosphorylation of Cdk1 (Lew and Reed, 1995; McMillan et al., 1998
; Rupes et al., 2001
; Sia et al., 1996
). Wee1-related kinases are therefore part of a mechanism that monitors successful completion of an actin-dependent event. Since actin is required for cell growth, actin depolymerization might cause a Wee1-dependent G2/M delay because cells fail to reach a critical size. To test this idea, Rupes et al. used the cdc25- mutant to arrest fission yeast cells in G2 phase (Rupes et al., 2001
). They kept the cells at the arrest point for varying periods to allow growth to different sizes and then released from the arrest in the presence of latrunculin A and assayed entry into mitosis. These experiments demonstrated that, once cells reach a critical size, they no longer undergo Wee1-dependent arrest in response to actin depolymerization (Rupes et al., 2001
). Similarly, experiments in budding yeast have shown that, once daughter buds pass a critical size, cells no longer arrest at G2/M in response to actin depolymerization (Harvey and Kellogg, 2003
). Taken together, these experiments are consistent with the idea that Wee1-related kinases function in a conserved checkpoint that monitors cell size or growth.
An alternative model proposed for budding yeast is that Swe1 functions in a bud morphogenesis checkpoint (Lew, 2000; McMillan et al., 1998
; Sia et al., 1996
; Sia et al., 1998
). According to this model, Swe1 monitors successful completion of bud emergence or the status of the actin cytoskeleton. The observation that actin depolymerization blocks bud emergence and induces a Swe1-dependent G2/M delay is consistent with this idea. Similarly, temperature-sensitive mutations that block bud emergence also induce a Swe1-dependent G2/M delay. However, several observations argue against the existence of a checkpoint that monitors bud morphogenesis or the status of the actin cytoskeleton. First, actin depolymerization induces a Swe1-dependent G2/M delay in cells that have already undergone bud emergence and formed a medium-sized bud (Harvey and Kellogg, 2003
; McMillan et al., 1998
). Thus, actin depolymerization induces a G2/M delay when morphogenesis of the bud is largely complete and the bud is simply increasing in size. Second, cells with daughter buds that have grown beyond a critical size no longer undergo a G2/M delay in response to actin depolymerization (Harvey and Kellogg, 2003
; McMillan et al., 1998
). These two observations argue against a checkpoint that simply monitors bud emergence or the status of the actin cytoskeleton.
The G2/M delay caused by mutants that fail to undergo bud emergence can also be explained by a G2/M cell-size checkpoint. Since cell growth after G1 phase occurs entirely in the daughter bud, one might predict that cell size at G2/M is monitored in the daughter bud, and that a signal is sent from the daughter bud once a critical size has been reached to trigger entry into mitosis (Hartwell and Unger, 1977; Karpova et al., 2000
). In cells that do not form a bud, such a signal would never be sent and cells should arrest at G2/M. Recent work has shown that daughter bud size has a strong influence on when cells enter mitosis, whereas mother cell size has no influence (Harvey and Kellogg, 2003
). These observations are consistent with the idea that cell size at G2/M is monitored specifically in the daughter bud. The idea that budding yeast monitor the size of the daughter bud at G2/M makes sense because cells must ensure that the daughter bud is large enough to accommodate the nucleus before nuclear division occurs. How might cells specifically monitor the size of the daughter bud? One possibility is that they measure the concentration of a molecule present only in the daughter bud. Such a molecule could be localized uniquely to the daughter bud through an association with actin patches, which are found predominantly in the daughter bud.
It is clear that we still have much to learn about the physiological functions of Wee1-related kinases in yeasts. An interesting model consistent with the data in both fission yeast and budding yeast is that Wee1-related kinases monitor the total amount of polar growth that occurs. Fission yeast are rod-shaped cells and all growth occurs at the ends of the cell (polar growth). By contrast, budding yeast undergo a brief period of polar growth during bud emergence, but then grow over the entire surface of the bud (isotropic growth). A role for Wee1-related kinases in monitoring polar growth could help explain why loss of function of Wee1 causes a much more severe phenotype in fission yeast, since fission yeast rely almost entirely on polar growth that occurs during G2, whereas budding yeast have only a brief period of polar growth and then switch to isotropic growth.
Fission yeast and animal cells have multiple Wee1-related kinases. Xenopus has a second Wee1 kinase called Wee2 (Leise and Mueller, 2002). Wee1 is expressed maternally, whereas Wee2 is expressed zygotically. Interestingly, Wee2 is expressed in non-dividing tissues and might therefore play a role in arresting the cell cycle at specific developmental stages (Leise and Mueller, 2002
). Fission yeast and vertebrates also each have a Wee1-related kinase: Mik1 and Myt1, respectively (Lundgren et al., 1991
; Mueller et al., 1995a
). In addition to phosphorylating the conserved tyrosine residue at the N-terminus of Cdk1, Myt1 can phosphorylate a neighboring threonine (Mueller et al., 1995a
). Loss of Mik1 alone has no phenotype in fission yeast, but mik1
strongly enhances wee1- mutants, which suggests that Mik1 has related functions (Lundgren et al., 1991
). Mik1 is also required in fission yeast for mediating a DNA damage checkpoint at G2/M (Furuya and Carr, 2003
; Rhind and Russell, 2001
). Since it is unclear whether these additional Wee1-related kinases are required for coordination of growth and division, their functions and regulation are not reviewed extensively here.
![]() |
Regulation of Wee1-related kinases |
---|
|
Experiments in fission yeast and budding yeast have identified several kinases required for regulation of Wee1-related kinases in vivo. The fission yeast kinases Cdr1/Nim1 and Cdr2 were identified in a screen for mutants that fail to adjust cell size properly in response to nitrogen limitation (Young and Fantes, 1987). Cdr1/Nim1 was independently identified in a screen for high-copy suppressors of a cdc25-ts allele (Russell and Nurse, 1987b
). Both cdr mutants undergo a prolonged G2/M delay that is eliminated in cdr wee1 double mutants, and overexpression of Cdr1 drives premature entry into mitosis (Breeding et al., 1998
; Feilotter et al., 1991
; Kanoh and Russell, 1998
; Russell and Nurse, 1987b
). These observations suggest that the Cdr kinases promote entry into mitosis by inhibiting Wee1 activity (Fig. 3). The Cdr kinases can directly phosphorylate Wee1 in vitro; however, it is not clear whether they phosphorylate Wee1 in vivo (Coleman et al., 1993
; Kanoh and Russell, 1998
; Parker et al., 1993
; Wu and Russell, 1993
).
In budding yeast, an intricate signaling network is required for regulation of Swe1 and for coordination of cell growth and cell division at G2/M (Fig. 4). This network includes the kinases Gin4, Hsl1, Cla4 and Elm1. In addition, a number of proteins that are required for regulation of these kinases have been identified, including Nap1, Hsl7, Cdc42 and a family of proteins called the septins (Altman and Kellogg, 1997; Barral et al., 1999
; Carroll et al., 1998
; Edgington et al., 1999
; Kellogg and Murray, 1995
; Longtine et al., 2000
; Ma et al., 1996
; Shulewitz et al., 1999
; Sreenivasan and Kellogg, 1999
; Tjandra et al., 1998
). Inactivation of this signaling network causes cells to undergo continuous polar growth during a prolonged G2/M delay, producing highly elongated cells that are abnormally large. The G2/M delay and cell elongation caused by inactivation of the network are reversed by deletion of the SWE1 gene. Furthermore, inactivation of the network leads to a failure to fully hyperphosphorylate Swe1 (Barral et al., 1999
; Longtine et al., 2000
; Ma et al., 1996
; Sreenivasan and Kellogg, 1999
). Finally, overexpression of Swe1 causes a G2/M arrest and a continuous polar growth phenotype that is similar to the phenotype caused by inactivation of the signaling network. Taken together, these observations argue that the signaling network is required for hyperphosphorylation and inactivation of Swe1 to allow entry into mitosis. However, it is unclear how the kinases in the signaling network regulate Swe1 because none of them has been found to phosphorylate Swe1 directly. In addition, the physiological signals that regulate the network are poorly understood, although there is some evidence that components of the network respond to nutritional cues (Cullen and Sprague, 2000
; Garrett, 1997
; La Valle and Wittenberg, 2001
). Many of the proteins that function in the network are highly conserved, suggesting that similar networks work in all eukaryotic cells. Gin4 and Hsl1, for example, are related to fission yeast Cdr1/Nim1 and Cdr2.
|
Biochemical and genetic experiments have identified physical interactions and functional relationships that connect the proteins in the signaling network that regulates Swe1 (Figs 4, 5). For example, Hsl7 associates with both Swe1 and Hsl1, although in separate complexes (McMillan et al., 1999; Shulewitz et al., 1999
). Gin4, Nap1 and the septins assemble into a complex during mitosis, which leads to hyperphosphorylation and activation of Gin4 (Mortensen et al., 2002
). Hsl1 also forms a complex with the septins and is activated in a septin-dependent manner (Barral et al., 1999
). Although the septins are required for Gin4 activation, Gin4 is required for septin organization, and Gin4 appears to control septin organization at least in part by direct phosphorylation of the Shs1 septin (Longtine et al., 1998
; Longtine et al., 2000
; Mortensen et al., 2002
). Interestingly, Gin4 and Elm1 were identified in a screen for substrates of a mitotic CDK complex composed of the Clb2 cyclin and Cdk1 (Ubersax and Morgan, 2003). In addition, hyperphosphorylation of both Gin4 and Cla4 appears to be dependent upon Cdk1 (Mortensen et al., 2002
; Tjandra et al., 1998
). These results suggest that the signaling network may be part of a positive-feedback loop initiated by mitotic Cdk1 to regulate Swe1. However, regulation of these kinases appears to be more complex than simple direct phosphorylation by Cdk1. For example, although Gin4 appears to be a direct substrate of Clb2/Cdk1, hyperphosphorylation of Gin4 in vivo is also dependent upon Elm1, Cla4, Nap1 and the septins (Altman and Kellogg, 1997
; Carroll et al., 1998
; Sreenivasan and Kellogg, 1999
; Tjandra et al., 1998
). The molecular mechanisms underlying these dependency relationships are largely unknown.
|
One can imagine two models for the functions of the signaling network. First, the network might directly regulate Swe1. For example, kinases in the network may directly phosphorylate Swe1 or inactivate phosphatases that act on Swe1. Alternatively, the network may be required for the successful completion of events that are monitored by Swe1 (Barral et al., 1999; Longtine et al., 2000
; Shulewitz et al., 1999
). According to this model, failure to complete these events would block full hyperphosphorylation of Swe1, thereby triggering a Swe1-dependent delay in cell-cycle progression until the events are successfully completed. At this point, however, it is difficult to distinguish which of these models applies without knowing more about the molecular mechanisms that regulate Swe1 or the physiological signals that trigger Swe1-dependent G2/M delays.
In vertebrate cells, 14-3-3 proteins have been found to bind and positively regulate Wee1-related kinases (Lee et al., 2001; Rothblum-Oviatt et al., 2001
; Wang et al., 2000
). However, there is no evidence yet that yeast homologs of 14-3-3 proteins play a role in regulation of Wee1-related kinases or in mechanisms required for coordination of cell growth and division at G2/M.
![]() |
Regulation of Wee1-related kinase protein levels |
---|
![]() |
Proteins required for regulation of Wee1-related kinases are likely to have additional functions |
---|
![]() |
Physiological roles of Cdc25-related phosphatases |
---|
Dephosphorylation of Cdk1 by Cdc25 appears to be a crucial rate-limiting step for entry into mitosis in at least some cells. In the Drosophila embryo, for example, entry into mitosis during the first few divisions that occur after cellularization requires transcription of Cdc25, and ectopic expression of Cdc25 can drive entry into mitosis (Edgar and O'Farrell, 1990). Furthermore, fission yeast cells in which Cdc25 has been replaced by a constitutively active tyrosine phosphatase enter mitosis prematurely when growth is inhibited by actin depolymerization (Rupes et al., 2001
). By contrast, inactivation of Wee1 and Mik1 does not cause premature entry into mitosis in cells that have been arrested in G2 phase by actin depolymerization. These results suggest that dephosphorylation of Cdk1 can be rate limiting for entry into mitosis in fission yeast, and that regulation of Cdc25 plays an important role in coordinating cell growth and cell division. In vertebrates and fission yeast, inhibition of Cdc25 in response to DNA damage plays an important role in enforcing the DNA damage checkpoint, which again demonstrates that regulation of Cdc25 can be limiting for entry into mitosis (Donzelli and Draetta, 2003
; Furnari et al., 1999
; Furnari et al., 1997
; Kumagai et al., 1998a
; Kumagai et al., 1998b
; Peng et al., 1997
; Rhind and Russell, 1998
; Sanchez et al., 1997
).
![]() |
Regulation of Cdc25-related phosphatases |
---|
![]() |
Future directions |
---|
![]() |
References |
---|
Aligue, R., Wu, L. and Russell, P. (1997). Regulation of Schizosaccharomyces pombe Wee1 tyrosine kinase. J. Biol. Chem. 272, 13320-13325.
Altman, R. and Kellogg, D. R. (1997). Control of mitotic events by Nap1 and the Gin4 kinase. J. Cell Biol. 138, 119-130.
Barral, Y., Parra, M., Bidlingmaier, S. and Snyder, M. (1999). Nim1-related kinases coordinate cell cycle progression with the organization of the peripheral cytoskeleton in yeast. Genes Dev. 13, 176-187.
Benton, B. K., Tinkelenberg, A. H., Jean, D., Plump, S. D. and Cross, F. R. (1993). Genetic analysis of Cln/Cdc28 regulation of cell morphogenesis in budding yeast. EMBO J. 12, 5267-5275.[Abstract]
Blasina, A., de Weyer, I. V., Laus, M. C., Luyten, W. H., Parker, A. E. and McGowan, C. H. (1999). A human homologue of the checkpoint kinase Cds1 directly inhibits Cdc25 phosphatase. Curr. Biol. 9, 1-10.[CrossRef][Medline]
Boddy, M. N., Furnari, B., Mondesert, O. and Russell, P. (1998). Replication checkpoint enforced by kinases Cds1 and Chk1. Science 280, 909-912.
Booher, R. N., Deshaies, R. J. and Kirschner, M. W. (1993). Properties of Saccharomyces cerevisiae wee1 and its differential regulation of p34CDC28 in response to G1 and G2 cyclins. EMBO J. 12, 3417-3426.[Abstract]
Bouquin, N., Barral, Y., Courbyrette, R., Blondel, M., Snyder, M. and Mann, C. (2000). Regulation of cytokinesis by the Elm1 protein kinase in Saccharomyces cerevisiae. J. Cell Sci. 113, 1435-1445.
Breeding, C. S., Hudson, J., Balasubramanian, M. K., Hemmingsen, S. M., Young, P. G. and Gould, K. L. (1998). The cdr2+ gene encodes a regulator of G2/M progression and cytokinesis in Schizosaccharomyces pombe. Mol. Biol. Cell 9, 3399-3415.
Carroll, C., Altman, R., Schieltz, D., Yates, J. and Kellogg, D. R. (1998). The septins are required for the mitosis-specific activation of the Gin4 kinase. J. Cell Biol. 143, 709-717.
Coleman, T. R., Tang, Z. and Dunphy, W. G. (1993). Negative regulation of the Wee1 protein kinase by direct action of the Nim1/Cdr1 mitotic inducer. Cell 72, 919-929.[Medline]
Cullen, P. J. and Sprague, G. F., Jr (2000). Glucose depletion causes haploid invasive growth in yeast. Proc. Natl. Acad. Sci. USA 97, 13619-13624.
Cvrckova, F. and Nasmyth, K. (1993). Yeast G1 cyclins CLN1 and CLN2 and a GAP-like protein have a role in bud formation. EMBO J. 12, 5277-5286.[Abstract]
Cvrckova, F., de Virgilio, C., Manser, E., Pringle, J. R. and Nasmyth, K. (1995). Ste20-like protein kinases are required for normal localization of cell growth and for cytokinesis in budding yeast. Genes Dev. 9, 1817-1830.[Abstract]
Donaldson, M. M., Tavares, A. A., Hagan, I. M., Nigg, E. A. and Glover, D. M. (2001). The mitotic roles of Polo-like kinase. J. Cell Sci. 114, 2357-2358.
Donzelli, M. and Draetta, G. F. (2003). Regulating mammalian checkpoints through Cdc25 inactivation. EMBO Rep. 4, 671-677.
Dunphy, W. G. and Kumagai, A. (1991). The cdc25 protein contains an intrinsic phosphatase activity. Cell 67, 189-196.[Medline]
Edgar, B. A. and O'Farrell, P. H. (1990). The three postblastoderm cell cycles of Drosophila embryogenesis are regulated in G2 by string. Cell 62, 469-480.[Medline]
Edgington, N. P., Blacketer, M. J., Bierwagen, T. A. and Myers, A. M. (1999). Control of Saccharomyces cerevisiae filamentous growth by cyclin-dependent kinase Cdc28. Mol. Cell. Biol. 19, 1369-1380.
Fantes, P. and Nurse, P. (1977). Control of cell size in fission yeast by a growth modulated size control over nuclear division. Exp. Cell Res. 107, 377-386.[Medline]
Fantes, P. A. and Nurse, P. (1978). Control of the timing of cell division in fission yeast. Cell size mutants reveal a second control pathway. Exp. Cell Res. 115, 317-329.[Medline]
Featherstone, C. and Russell, P. (1991). Fission yeast p107wee1 mitotic inhibitor is a tyrosine/serine kinase. Nature 349, 808-811.[CrossRef][Medline]
Feilotter, H., Nurse, P. and Young, P. (1991). Genetic and molecular analysis of cdr1/nim1 in Schizosaccaromyces pombe. Genetics 127, 309-318.
Furnari, B., Rhind, N. and Russell, P. (1997). Cdc25 mitotic inducer targeted by chk1 DNA damage checkpoint kinase. Science 277, 1495-1497.
Furnari, B., Blasina, A., Boddy, M. N., McGowan, C. H. and Russell, P. (1999). Cdc25 inhibited in vivo and in vitro by checkpoint kinases Cds1 and Chk1. Mol. Biol. Cell 10, 833-845.
Furuya, K. and Carr, A. M. (2003). DNA checkpoints in fission yeast. J. Cell Sci. 116, 3847-3848.
Garrett, J. M. (1997). The control of morphogenesis in Saccharomyces cerevisiae by Elm1 kinase is responsive to RAS/cAMP pathway activity and tryptophan availability. Mol. Microbiol. 26, 809-820.[CrossRef][Medline]
Gautier, J., Solomon, M. J., Booher, R. N., Bazan, J. F. and Kirschner, M. W. (1991). cdc25 is a specific tyrosine phosphatase that directly activates p34cdc2. Cell 67, 197-211.[Medline]
Gould, K. L. and Nurse, P. (1989). Tyrosine phosphorylation of the fission yeast cdc2+ protein kinase regulates entry into mitosis. Nature 342, 39-45.[CrossRef][Medline]
Hartwell, L. H. and Unger, M. W. (1977). Unequal division in Saccharomyces cerevisiae and its implications for the control of cell division. J. Cell Biol. 75, 422-435.[Abstract]
Harvey, S. L. and Kellogg, D. R. (2003). Conservation of mechanisms controlling entry into mitosis: budding yeast wee1 delays entry into mitosis and is required for cell size control. Curr. Biol. 13, 264-275.[CrossRef][Medline]
Izumi, T. and Maller, J. L. (1993). Elimination of cdc2 phosphorylation sites in the cdc25 phosphatase blocks initiation of M-phase. Mol. Biol. Cell 12, 1337-1350.
Izumi, T., Walker, D. H. and Maller, J. L. (1992). Periodic changes in the phosphorylation of the Xenopus Cdc25 phosphatase regulate its activity. Mol. Biol. Cell 3, 927-939.[Abstract]
Johnston, G. C., Pringle, J. R. and Hartwell, L. H. (1977). Coordination of growth with cell division in the yeast Saccharomyces cervisiae. Exp. Cell. Res. 105, 79-98.[Medline]
Jorgensen, P., Nishikawa, J. L., Breitkreutz, B. J. and Tyers, M. (2002). Systematic identification of pathways that couple cell growth and cell division in yeast. Science 297, 395-400.
Kanoh, J. and Russell, P. (1998). The protein kinase Cdr2, related to Nim1/Cdr1 mitotic inducer, regulates the onset of mitosis in fission yeast. Mol. Biol. Cell 9, 3321-3334.
Karpova, T. S., Reck-Peterson, S. L., Elkind, N. B., Mooseker, M. S., Novick, P. J. and Cooper, J. A. (2000). Role of actin and Myo2p in polarized secretion and growth of Saccharomyces cerevisiae. Mol. Biol. Cell 11, 1727-1737.
Kellogg, D. R. and Murray, A. W. (1995). NAP1 acts with Clb2 to perform mitotic functions and suppress polar bud growth in budding yeast. J. Cell Biol. 130, 675-685.[Abstract]
Kumagai, A. and Dunphy, W. G. (1991). The cdc25 protein controls tyrosine dephosphorylation of the cdc2 protein in a cell-free system. Cell 64, 903-914.[Medline]
Kumagai, A. and Dunphy, W. G. (1992). Regulation of the cdc25 protein during the cell cycle in Xenopus extracts. Cell 70, 139-151.[Medline]
Kumagai, A. and Dunphy, W. (1996). Purification and molecular cloning of Plx1, a Cdc25-regulatory kinase from Xenopus egg extracts. Science 273, 1377-1380.[Abstract]
Kumagai, A., Guo, Z., Emami, K. H., Wang, S. X. and Dunphy, W. G. (1998a). The Xenopus Chk1 protein kinase mediates a caffeine-sensitive pathway of checkpoint control in cell-free extracts. J. Cell Biol. 142, 1559-1569.
Kumagai, A., Yakowec, P. S. and Dunphy, W. G. (1998b). 14-3-3 proteins act as negative regulators of the mitotic inducer Cdc25 in Xenopus egg extracts. Mol. Biol. Cell 9, 345-354.
La Valle, R. and Wittenberg, C. (2001). A role for the Swe1 checkpoint kinase during filamentous growth of Saccharomyces cerevisiae. Genetics 158, 549-562.
Lee, J., Kumagai, A. and Dunphy, W. G. (2001). Positive regulation of Wee1 by Chk1 and 14-3-3 proteins. Mol. Biol. Cell 12, 551-563.
Lee, M. S., Ogg, S., Xu, M., Parker, L. L., Donoghue, D. J., Maller, J. L. and Piwnica-Worms, H. (1992). cdc25+ encodes a protein phosphatase that dephosphorylates p34cdc2. Mol. Biol. Cell 3, 73-84.[Abstract]
Leise, W., 3rd and Mueller, P. R. (2002). Multiple Cdk1 inhibitory kinases regulate the cell cycle during development. Dev. Biol. 249, 156-173.[CrossRef][Medline]
Lew, D. J. (2000). Cell-cycle checkpoints that ensure coordination between nuclear and cytoplasmic events in Saccharomyces cerevisiae. Curr. Opin. Genet. Dev. 10, 47-53.[CrossRef][Medline]
Lew, D. and Reed, S. I. (1995). A cell cycle checkpoint monitors cell morphogenesis in budding yeast. J. Cell Biol. 129, 739-749.[Abstract]
Longtine, M. S., Fares, H. and Pringle, J. (1998). Role of the yeast Gin4p protein kinase in septin assembly and the relationship between septin assembly and septin function. J. Cell Biol. 143, 719-736.
Longtine, M. S., Theesfeld, C. L., McMillan, J. N., Weaver, E., Pringle, J. R. and Lew, D. J. (2000). Septin-dependent assembly of a cell cycle-regulatory module in Saccharomyces cerevisiae. Mol. Cell. Biol. 20, 4049-4061.
Lundgren, K., Walworth, N., Booher, R., Dembski, M., Kirschner, M. and Beach, D. (1991). mik1 and wee1 cooperate in the inhibitory tyrosine phosphorylation of cdc2. Cell 64, 1111-1122.[Medline]
Ma, J. X., Lu, Q. and Grunstein, M. (1996). A search for proteins that interact genetically with histone H3 and H4 amino termini uncovers novel regulators of the Swe1 kinase in Saccharomyces cerevisiae. Genes Dev. 10, 1327-1340.[Abstract]
McMillan, J. N., Sia, R. A. L. and Lew, D. J. (1998). A morphogenesis checkpoint monitors the actin cytoskeleton in yeast. J. Cell Biol. 142, 1487-1499.
McMillan, J. N., Longtine, M. S., Sia, R. A. L., Theesfeld, C. L., Bardes, E. S. G., Pringle, J. R. and Lew, D. J. (1999). The morphogenesis checkpoint in Saccharomyces cerevisiae: cell cycle control of Swe1p degradation by Hsl1p and Hsl7p. Mol. Cell. Biol. 19, 6929-6939.
McMillan, J. N., Theesfeld, C. L., Harrison, J. C., Bardes, E. S. and Lew, D. J. (2002). Determinants of Swe1p degradation in Saccharomyces cerevisiae. Mol. Biol. Cell 13, 3560-3575.
Millar, J. B., McGowan, C. H., Lenaers, G., Jones, R. and Russell, P. (1991). p80cdc25 mitotic inducer is the tyrosine phosphatase that activates p34cdc2 kinase in fission yeast. EMBO J. 10, 4301-4309.[Abstract]
Mortensen, E., McDonald, H., Yates, J. and Kellogg, D. R. (2002). Cell cycle-dependent assembly of a Gin4-septin complex. Mol. Biol. Cell 13, 2091-2105.
Mueller, P. R., Coleman, T. R., Kumagai, A. and Dunphy, W. G. (1995a). Myt1: a membrane-associated inhibitory kinase that phosphorylates Cdc2 on both threonine-14 and tyrosine-15. Science 270, 86-90.[Abstract]
Mueller, P. R., Coleman, T. R. and Dunphy, W. G. (1995b). Cell cycle regulation of a Xenopus wee1-like kinase. Mol. Biol. Cell 6, 119-134.[Abstract]
Nurse, P. (1975). Genetic control of cell size at cell division in yeast. Nature 256, 547-551.[Medline]
Parker, L. L. and Piwnica-Worms, H. (1992). Inactivation of the p34cdc2-cyclin B complex by the human WEE1 tyrosine kinase. Science 257, 1955-1957.[Medline]
Parker, L. L., Atherton-Fessler, S. and Piwnica-Worms, H. (1992). p107wee1 is a dual-specificity kinase that phosphorylates p34cdc2 on tyrosine 15. Proc. Natl. Acad. Sci. USA 89, 2917-2921.[Abstract]
Parker, L. L., Walter, S. A., Young, P. G. and Piwnica-Worms, H. (1993). Phosphorylation and inactivation of the mitotic inhibitor Wee1 by the nim1/cdr1 kinase. Nature 363, 736-738.[CrossRef][Medline]
Peng, C. Y., Graves, P. R., Thoma, R. S., Wu, Z., Shaw, A. S. and Piwnica-Worms, H. (1997). Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216. Science 277, 1501-1505.
Qian, Y. W., Erikson, E., Taieb, F. E. and Maller, J. (2001). The polo-like kinase Plx1 is required for activation of the phosphatase Cdc25c and CyclinB-Cdc2 in Xenopus oocytes. Mol. Biol. Cell 12, 1791-1799.
Rhind, N. and Russell, P. (1998). Tyrosine phosphorylation of cdc2 is required for the replication checkpoint in Schizosaccharomyces pombe. Mol. Cell. Biol. 18, 3782-3787.
Rhind, N. and Russell, P. (2001). Roles of the mitotic inhibitors Wee1 and Mik1 in the G2 DNA damage and replication checkpoints. Mol. Cell. Biol. 21, 1499-1508.
Rothblum-Oviatt, C. J., Ryan, C. E. and Piwnica-Worms, H. (2001). 14-3-3 binding regulates catalytic activity of human Wee1 kinase. Cell Growth Differ. 12, 581-589.
Rupes, I. (2002). Checking cell size in yeast. Trends Genet. 18, 479-485.[CrossRef][Medline]
Rupes, I., Webb, B. A., Mak, A. and Young, P. G. (2001). G2/M arrest caused by actin disruption is a manifestation of the cell size checkpoint in fission yeast. Mol. Biol. Cell 12, 3892-3903.
Russell, P. and Nurse, P. (1986). cdc25+ functions as an inducer in the mitotic control of fission yeast. Cell 45, 145-153.[Medline]
Russell, P. and Nurse, P. (1987a). Negative regulation of mitosis by wee1+, a gene encoding a protein kinase homolog. Cell 49, 559-567.[Medline]
Russell, P. and Nurse, P. (1987b). The mitotic inducer nim1+ functions in a regulatory network of protein kinase homologs controlling the initiation of mitosis. Cell 49, 569-576.[Medline]
Russell, P., Moreno, S. and Reed, S. I. (1989). Conservation of mitotic controls in fission and budding yeasts. Cell 57, 295-303.[Medline]
Sanchez, Y., Wong, C., Thoma, R. S., Richman, R., Wu, Z., Piwnica-Worms, H. and Elledge, S. J. (1997). Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25. Science 277, 1497-1501.
Shulewitz, M. J., Inouye, C. J. and Thorner, J. (1999). Hsl7 localizes to a septin ring and serves as an adapter in regulatory pathway that relieves tyrosine phosphorylation of Cdc28 protein kinase in Saccharomyces cerevisiae. Mol. Cell. Biol. 19, 7123-7137.
Sia, R. A., Herald, H. A. and Lew, D. J. (1996). Cdc28 tyrosine phosphorylation and the morphogenesis checkpoint in budding yeast. Mol. Biol. Cell 11, 1657-1666.
Sia, R. A. L., Bardes, E. S. G. and Lew, D. J. (1998). Control of Swe1p degradation by the morphogenesis checkpoint. EMBO J. 17, 6678-6688.
Sreenivasan, A. and Kellogg, D. (1999). The Elm1 kinase functions in a mitotic signaling network in budding yeast. Mol. Cell. Biol. 19, 7983-7994.
Sreenivasan, A., Bishop, A., Shokat, K. and Kellogg, D. (2003). Specific inhibition of Elm1 kinase activity reveals functions required for early G1 events. Mol. Cell. Biol. 23, 6327-6337.
Strausfeld, U., Labbé, J. C., Fesquet, D., Cavadore, J. C., Picard, A., Sadhu, K., Russell, P. and Dorée, M. (1991). Dephosphorylation and activation of a p34cdc2/cyclin B complex in vitro by human CDC25 protein. Nature 351, 242-245.[CrossRef][Medline]
Tanaka, K., Petersen, J., MacIver, F., Mulvihill, D. P., Glover, D. and Hagan, I. M. (2001). The role of Plo1 kinase in mitotic commitment and septation in Schizosaccharomyces pombe. EMBO J. 20, 1259-1270.
Tang, Z., Coleman, T. R. and Dunphy, W. G. (1993). Two distinct mechanisms for the negative regulation of the Wee1 protein kinase. EMBO J. 12, 3427-3436.[Abstract]
Thornton, B. R. and Toczyski, D. (2003). Cycling without the cyclosome: securin and B-cyclin/CDK are the only essential targets of the APC. Nat. Cell Biol. (in press).
Thuriaux, P., Nurse, P. and Carter, B. (1978). Mutants altered in the control co-ordinating cell division with cell growth in the fission yeast Schizosaccharomyces pombe. Mol. Gen. Genet. 161, 215-220.[Medline]
Tjandra, H., Compton, J. and Kellogg, D. R. (1998). Control of mitotic events by the Cdc42 GTPase, the Clb2 cyclin and a member of the PAK kinase family. Curr. Biol. 8, 991-1000.[Medline]
Ubersax, J. A., Woodbury, E. L., Quang, P. N., Paraz, M., Blethrow, J. D., Shah, K., Shokat, K. M. and Morgan, D. O. (2003). Targets of the cyclin-dependent kinase Cdk1. Nature 425, 859-864.[CrossRef][Medline]
Walter, S. A., Guadagno, S. N. and Ferrell, J. E. J. (2000). Activation of Wee1 by p42 MAPK in vitro and in cycling Xenopus egg extracts. Mol. Biol. Cell 11, 887-896.
Wang, Y., Jacobs, C., Hook, K. E., Duan, H., Booher, R. N. and Sun, Y. (2000). Binding of 14-3-3beta to the carboxyl terminus of Wee1 increases Wee1 stability, kinase activity, and G2-M cell population. Cell Growth Differ. 11, 211-219.
Wu, L. and Russell, P. (1993). Nim1 kinase promotes mitosis by inactivating Wee1 tyrosine kinase. Nature 363, 738-741[CrossRef][Medline]
Young, P. G. and Fantes, P. A. (1987). Schizosaccharomyces pombe mutants affected in their division response to starvation. J. Cell Sci. 88, 295-304.[Abstract]
Zimmerman, Z. and Kellogg, D. R. (2001). The Sda1 protein is required for passage through Start. Mol. Biol. Cell 12, 201-219.