HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nishizawa, M. Articles by Toh-e, A. Search for Related Content PubMed PubMed Citation Articles by Nishizawa, M. Articles by Toh-e, A. Social Bookmarking                      What's this?

J Biol Chem, Vol. 274, Issue 48, 33859-33862, November 26, 1999

COMMUNICATION
Mouse Cyclin-dependent Kinase (Cdk) 5 Is a Functional Homologue of a Yeast Cdk, Pho85 Kinase^*

Masafumi Nishizawa^§, Yuko Kanaya, and Akio Toh-e^¶

From the  Department of Microbiology, Keio University School of Medicine, Shinjuku, Tokyo 160-8582 and the ^¶ Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo, Tokyo 113-0033, Japan

	ABSTRACT

TOP ABSTRACT INTRODUCTION EXPERIMENTAL PROCEDURES RESULTS AND DISCUSSION REFERENCES

Mouse cyclin-dependent kinase (Cdk) 5 and yeast Pho85 kinase share similarities in structure as well as in the regulation of their activity. We found that mouse Cdk5 kinase produced in pho85 mutant cells could suppress some of pho85 mutant phenotypes including failure to grow on nonfermentable carbon sources, morphological defects, and growth defect caused by Pho4 or Clb2 overproduction. We also demonstrated that Cdk5 coimmunoprecipitated with Pho85-cyclins including Pcl1, Pcl2, Pcl6, Pcl9, and Pho80, and that the immunocomplex could phosphorylate Pho4, a native substrate of Pho85 kinase. Thus mouse Cdk5 is a functional homologue of yeast Pho85 kinase.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION EXPERIMENTAL PROCEDURES RESULTS AND DISCUSSION REFERENCES

Cyclin-dependent kinase (Cdk)¹ plays a key regulatory role in the progression of the cell cycle. Vertebrate cells have various Cdks (Cdk1 to Cdk8) and cyclins (cyclins A, B, C, D, E, and H), and their different combinations are utilized at different stages of the cell cycle (1), whereas in budding yeast, a unique Cdk, Cdc28 kinase, functions by associating with distinct cyclins (2). Budding yeast also has a Cdk family whose members, including Pho85, Kin28, and Srb10 kinases, function in various cellular events (3-5).

Among mammalian Cdk family members, Cdk5 is not yet demonstrated to be involved in cell proliferation. Cdk5, activated by binding of p35 subunit (6), plays an important role in control of neurogenesis, including neurite outgrowth, axon guidance, and cell migration (7, 8). Cdk5 and yeast Pho85 kinases share 57% identity in the amino acid sequence (9, 10), and Pho85 has a pleiotropic function including response to nutrient conditions (11-13), PLC1-pathway (14), aminoglycoside sensitivity (15), and cell cycle regulation (16-19). Regulation of the two kinases appears similar: they are not further activated by Cdk-activating kinase (20-22), and substitutions of Ser-159 of Cdk5 and Ser-166 of Pho85 in the T-loop with alanine do not affect the kinase activities, whereas phosphorylation of Tyr-15 of Cdk5 and Tyr-18 of Pho85 appears to enhance binding of p35 and Pho80, respectively (23).², ³ These similarities prompted us to test whether mouse Cdk5 kinase expressed in yeast cells can substitute Pho85 kinase and interact with Pho85-cyclins. Here we report that mouse Cdk5 kinase can suppress some of pho85 mutant phenotypes and can associate with Pho85-cyclins, including Pcl1, Pcl2, Pcl6, Pcl9, and Pho80, to phosphorylate Pho4. Thus mouse Cdk5 kinase is a functional homologue of yeast Pho85 kinase.

	EXPERIMENTAL PROCEDURES

TOP ABSTRACT INTRODUCTION EXPERIMENTAL PROCEDURES RESULTS AND DISCUSSION REFERENCES

Strains and MediaYeast strains used were MFY115 (MAT leu2 ura3 trp1 ade1 his GAL⁺), MFY116 (MFY115 pho85::LEU2), MFY121 (MATa leu2 ura3 trp1 ade1 his GAL⁺ pho85::URA3), and MFY151 (MATa ade2-1 trp1-1 leu2-3, 112 his3-11, 15 ura3 GAL cln1::hisG cln2 METp-CLN2(TRP1) pho85::LEU2) (19). MFY164 (pho85) was derived from MFY121 by selecting a resistant to 5-fluoro-orotic acid (24) and was used to construct double mutants with pcl1 (MFY165), pcl2 (MFY175), pcl6 (MFY166), pcl9 (MFY167), or pho80 (MFY168). Yeast cells were grown in SD medium containing 0.67% Difco Yeast Nitrogen Base, 2% glucose, and appropriate nutritional supplements (25); SGal medium where galactose replaces glucose in SD; or SGlyLac medium where glycerol plus lactate replace glucose.

Polymerase chain reaction Cloning and Construction of Plasmids-- Cloning of PCL1, PCL2, CLB2, and PHO80 was described previously (19). DNA fragments encoding PCL6 or PCL9 were similarly cloned (19): the primers were synthesized to incorporate an NcoI site at the start codon of PCL6 (5'-AAATAGCGGCGCCATGGCTATCAAAGG) or an EcoRI site immediately downstream of the start codon of PCL9 (5'-CACAAAGAGATGAATTCTGACTACGAT) and a BglII site at the 3'-end of each ORF (5'-CATATTACGCATTTAGATCTGCCCGTAACTAG for PCL6 and 5'-GGCGAGTAACTTAAGATCTTTGCTTGAAAAACG for PCL9). These fragments were incorporated into pMF906 (19), together with a TRP1 marker, to produce HA-cyclins under the control of the GAL10 promoter. To disrupt genomic loci of these cyclins, a TRP1 fragment was used to replace an EcoRV-SalI fragment of PCL1, an SspI-SspI fragment of PCL2, a BamHI-XbaI fragment of PCL6, and an NcoI-EcoRV fragment of PCL9, and a LEU2 fragment was to replace a ClaI-XbaI fragment of PHO80. Successful disruption was confirmed by polymerase chain reaction. A cDNA clone encoding mouse Cdk5 kinase (26) and a URA3 marker were cloned into pMF906 plasmid to generate pMF1086. The cDNA fragment was also incorporated into pMF568 (URA3) to generate pMF1057 in which the kinase was produced under the control of the PYK1 promoter (27). Plasmid pMF1079 consists of a BamHI-SalI fragment containing the promoter and the ORF of PHO85² and a URA3 marker. To overproduce Pho4 and Clb2 proteins, DNA fragments encoding each protein were cloned into pMF906, together with a TRP1 or a LEU2 marker to generate pMF869 (GAL10-PHO4-TRP1), pMF1084 (GAL10-PHO4-LEU2), pMF922 (GAL10-CLB2-TRP1), and pMF1085 (GAL10-CLB2-LEU2).

Analysis of Mutant Phenotypes and Its Suppression-- Utilization of nonfermentable carbon source, production of acid phosphatase, and accumulation of glycogen were assayed as described (11, 12, 28). Suppression of growth arrest of a cln1 cln2 pho85 triple mutant was tested with strain MFY151 as described (19). Morphological defects were microscopically observed with overnight culture, and cell number was counted with a hemocytometer. Suppression of growth defect caused by overproduction of Pho4 or Clb2 proteins was analyzed by streaking yeast transformants on SD and SGal media supplemented with nutrients but lacking uracil and leucine. For spotting cell suspension, overnight culture of yeast transformants were adjusted to ~5 × 10⁷ cells/ml, and serial 10-fold dilutions of the suspension were plated on SD and SGal media supplemented with nutrients but lacking uracil, leucine, and tryptophan.

Immunoprecipitation and Kinase Assay-- Preparation of cell extracts, immunoprecipitation, and kinase assay were as described (19). Briefly, after the induction of the production of HA-cyclin and Cdk5 in SGal medium at 30 °C for 3 h, the extracts were prepared from cells suspended in lysis buffer by vortexing with glass beads (0.45-mm diameter). To 50 µl of the extract containing ~200 µg of protein, 1 µl of anti-HA monoclonal antibody (HAmAb; clone 16B12, Berkeley Antibody Company) or 1 µl of anti-GST antibody (GST Ab) was added, and the mixture was incubated on ice for 1 h. The immunocomplex was recovered by absorbing with Protein A-Sepharose 6B (Amersham Pharmacia Biotech) for 1 h at 4 °C, washed three times with radioimmunoprecipitation assay buffer (lysis buffer supplemented with 150 mM NaCl) and twice with kinase assay buffer, and subjected to kinase assay using Pho4, Sic1, or histone H1 as substrate. Immunoblotting of Cdk5 and HA-cyclins were performed essentially as described (19) using anti-Cdk5 monoclonal antibody (a gift of G. Patrick and L.-H. Tsai) at 1:500 dilution and HAmAb at 1:1000 dilution, respectively.

	RESULTS AND DISCUSSION

TOP ABSTRACT INTRODUCTION EXPERIMENTAL PROCEDURES RESULTS AND DISCUSSION REFERENCES

Suppression of pho85 Mutant Phenotypes by Cdk5-- Among pleiotropic pho85 mutant phenotypes, we tested constitutive expression of acid phosphatase (11), growth arrest of a cln1 cln2 pho85 triple mutant (16, 17), accumulation of glycogen (12, 13), failure to grow on nonfermentable carbon sources (13, 28), abnormal morphology (29), and growth arrest caused by Pho4 or Clb2 overproduction (this work). Overproduction of mouse Cdk5 kinase failed to suppress the first three phenotypes (Fig. 1) but could suppress the other mutant phenotypes (Figs. 2 and 3). Cdk5 could restore growth of pho85 cells on glycerol + lactate medium (Fig. 2A). Overproduction of Pho4 or Clb2 proteins directed by the GAL10 promoter caused a growth defect in the absence of Pho85 kinase, which was suppressed by overproduction of Cdk5 kinase (Fig. 2B). Overproduction of Cdk5 itself did not affect the growth of pho85 cells (Fig. 2B). pho85 mutant cells become large (29) and show an apparent defect in separation of daughter cells, resulting in multiple-budded cells (Fig. 3A). They did not separate after extensive sonication under which conditions the wild-type cells did. The ratio of cells with morphological defects to the total cells reached ~33% in pho85 cells, which was decreased to 1.8% by expression of PHO85 and to 3.8% by that of CDK5 (Fig. 3A). Thus Cdk5 could function in yeast to suppress some of pho85 mutant phenotypes.

View larger version (81K): [in this window] [in a new window]   Fig. 1.   pho85 mutant phenotypes not suppressed by mouse Cdk5 kinase. Phenotypes studied and tested strains (MFY115 and MFY116) harboring plasmids producing Pho85 (pMF1079), Cdk5 (pMF1057), or vector (pMF558) are as indicated. Cells producing acid phosphatase encoded by PHO5 and those accumulating glycogen are stained dark.

View larger version (50K): [in this window] [in a new window]   Fig. 2.   pho85 mutant phenotypes suppressed by mouse Cdk5 kinase including inability to grow on glycerol plus lactate (A) and growth defect caused by overproduction of Pho4 or Clb2 (B). In panel A, combinations of tested strains (MFY115 and MFY116) and plasmids expressing CDK5 (pMF1057), PHO85 (pMF1079), or vector (pMF558) are as indicated. In panel B, combinations of plasmids introduced into pho85 cells (MFY164) are similarly indicated. Pho4 (pMF1084), Clb2 (pMF1085), and Cdk5 (pMF1086) were overproduced under the control of the GAL10 promoter.

View larger version (44K): [in this window] [in a new window]   Fig. 3.   Abnormal morphology of pho85 cells and its suppression by Cdk5 kinase (A) and the effect of a deletion of individual Pho85-cyclin gene on the suppression efficiency (B). About 300 cells were counted to determine the ratio of cells with morphological defects in individual experiments. The data shown are an average of three separate experiments and standard errors were ±1% for PHO85+, +Pho85, or +Cdk5, and ±5% for +vector experiments. A, the combination of strains (MFY115 and MFY116) and plasmids (pMF558, pMF1079, and pMF1057) are as indicated. B, each line shows the ratio of cells with morphological defects in double mutants (MFY165, MFY176, MFY166, MFY167, and MFY168) harboring vector alone (pMF558), Pho85- (pMF1079), or Cdk5- (pMF1057) producing plasmids.

Cdk5 Kinase Can Phosphorylate Pho4 in Vitro-- Ten cyclin-like proteins are known to interact with Pho85, and among them Pho85 complexed with Pcl1, Pcl2, Pcl9, Pcl10, or Pho80 was shown to phosphorylate Pho4 in vitro (16-18, 30, 31). These facts led us to a hypothesis that Cdk5 may associate with Pho85-cyclin(s) to phosphorylate Pho4, resulting in suppression of the growth defect caused by Pho4 overproduction. To test this idea, we first immunoprecipitated Cdk5 from yeast extracts and assayed its kinase activity on Pho4, Sic1, and histone H1. As shown in Fig. 4A, immunoprecipitated Cdk5 could phosphorylate Pho4 and histone H1, with more efficient phosphorylation of the latter (lanes 1 and 3), but failed to phosphorylate Sic1 to a detectable level (lane 2). Pho85 kinase, on the other hand, could phosphorylate Pho4 and Sic1 but not histone H1 (lanes 6-8). Control experiments (lanes 4 and 5) did not give a detectable level of Pho4 phosphorylation. These results demonstrate that Cdk5 kinase can phosphorylate Pho4 as well as histone H1 in vitro.

View larger version (41K): [in this window] [in a new window]   Fig. 4.   Mouse Cdk5 kinase can phosphorylate Pho4 and form a complex with Pho85-cyclins. A, activities of Cdk5 and Pho85 kinases in vitro. Cdk5 and GST-Pho85 were immunoprecipitated from cell extracts of MFY116 with anti-Cdk5 and GST Ab, respectively, and the immunoprecipitates were subjected to kinase assay. The bands corresponding to phosphorylated substrates are indicated. B, coimmunoprecipitation of Cdk5 with Pho85-cyclins and kinase activity of the immunocomplex on Pho4. Extracts were prepared from MFY161 cells producing Cdk5 and individual HA-cyclin, and the epitope-tagged cyclin was precipitated with HAmAb. The immunoprecipitates were then subjected to kinase assay with Pho4 as substrate and to immunoblotting with anti-Cdk5 Ab to detect the presence of Cdk5 in the immunocomplex. C, presence of individual HA-tagged Pho85-cyclins in the extracts used for the coimmunoprecipitation experiment was analyzed by loading ~40 µg of proteins onto SDS-polyacrylamide gel, followed by immunoblotting with HAm Ab. Positions of molecular weight marker proteins are designated at the left side of the panel.

We next studied an interaction of Cdk5 with Pho85-cyclins by coimmunoprecipitation from cell extracts prepared from pho85 cells overproducing Cdk5 and either HA-Pcl1, -Pcl2, -Pcl6, -Pcl9, or -Pho80. Any combination of the Pho85-cyclins and Cdk5 kinase could phosphorylate Pho4, and Pcl2-Cdk5 appeared most efficient (Fig. 4B, lane 10, top panel). The observation that Cdk5 was detected in the immunocomplexes with Pcl1, Pcl2, Pcl6, Pcl9, or Pho80 suggests that the kinase can interact with these Pho85-cyclins in yeast cells (Fig. 4B, lanes 9-13, bottom panel). Western blotting analysis of the cell extracts demonstrated that there were no significant differences in the amount of HA-cyclins in the extracts (Fig. 4C).

Possible Cyclin Partner of Cdk5 in Yeast-- It is believed that combination with different cyclins is responsible for distinct Pho85 function (31). For example, Pho80-Pho85 phosphorylates Pho4 to repress PHO5 expression (30); Pcl8, Pcl10-Pho85 acts on Gsy2 to regulate glycogen synthesis (31); and Pcl1-Pho85 phosphorylates Sic1 for its prompt degradation (19). Therefore, Cdk5 may associate with specific Pho85-cyclin(s) to suppress different pho85 mutant phenotypes. To answer this, we analyzed Cdk5 function in double mutant cells where pho85 was combined with pcl1, pcl2, pcl6, pcl9, or pho80 mutations.

With respect to morphological defects of the double mutants, Cdk5 kinase could reduce the ratio of cells with abnormal shape, but not as efficiently as in pho85 single mutant cells, and a deletion of PCL1 or PCL9 appeared to result in less efficient suppression than did that of the other cyclin genes (Fig. 3B). Expression of Pho85 kinase in the double mutants gave similar effect. These results suggest that cyclin(s) other than those tested may be required for Pho85 and Cdk5 to affect cell morphology or that cyclins interacting with either kinase to regulate cell morphology are redundant although individual cyclin may contribute to the suppression to a different extent.

Next we tested suppression of the growth defect caused by overproduction of Pho4 or Clb2 in the double mutants. As shown in Fig. 5, overproduction of these proteins caused the growth defect in the double mutants as well as in pho85 single mutant, and even in the wild-type cells (Fig. 5, panels B1 and B2). These single or double mutants could grow normally on galactose medium (panel B3). Overproduction of Cdk5 together with Pho4 could restore the growth of pho85 and the wild-type cells (Fig. 5, panel C1). The suppression by Cdk5 appeared dependent on a specific Pho85-cyclin: the absence of Pcl1, Pcl6, Pcl9, or Pho80 did not appear to affect the suppression efficiency, whereas that of Pcl2 resulted in almost no suppression by Cdk5 kinase (panel C1), suggesting that the Pcl2-Cdk5 complex may be most crucial to overcome the growth defect. To the contrary, Pho85 kinase did not show a specific requirement of cyclin to counteract the effect of Pho4 overproduction: the double and pho85 single mutants showed similar level of growth recovery by Pho85 (panel D1).

View larger version (90K): [in this window] [in a new window]   Fig. 5.   Effect of a deletion of individual Pho85-cyclin gene on the suppression by Cdk5 (pMF1086) or Pho85 (pMF1079) of the growth defect caused by overproduction of Pho4 (pMF869 or pMF1084; panel 1) or Clb2 (pMF922 or pMF1085; panel 2). Each cell suspension was adjusted to ~5 × 107 cells/ml, and serial 10-fold dilutions were spotted on SD or SGal medium supplemented with nutrients but lacking uracil, leucine, and tryptophan. The relevant genotypes of strains (MFY115, MFY164, MFY165, MFY175, MFY166, MFY167, and MFY168) and a combination of plasmids introduced into each strain are as indicated.

In the case of the growth defect caused by Clb2 overproduction, Cdk5 showed very weak suppression in the pho85 pcl6 mutant, whereas, in the other double mutants, it could suppress the defect as efficiently as in pho85 single mutant (panel C2), suggesting that Cdk5 may be highly dependent on Pcl6 to counteract the overproduction effect of Clb2. This is in clear contrast to the function of Pho85 where PCL6 was dispensable (panel D2), whereas the other Pho85-cyclins tested might individually contribute to the Pho85 function to a certain extent (panel D2). Overproduction of Cdk5 or Pho85 alone did not affect the growth of strains tested (panels C3 and D3). Taken together, these results suggest that the suppression by Cdk5 of the growth defect caused by Pho4 or Clb2 was dependent on a specific Pho85-cyclin.

In this paper we demonstrated that mouse Cdk5 kinase could suppress some of pho85 mutant phenotypes. This limited function could stem from defective interaction with some Pho85-cyclins and/or from failure to phosphorylate appropriate substrates to a sufficient level. We could detect, by coimmunoprecipitation, an interaction of Cdk5 with Pcl1, Pcl2, Pcl6, Pcl9, or Pho80 (Fig. 4B), but Cdk5 function in vivo appeared to be dependent on specific Pho85-cyclins, as observed in the suppression of the growth defect caused by Pho4 or Clb2 overproduction (Fig. 5). Thus it is formally possible that Cdk5 fails to interact with specific cyclin(s) in vivo, resulting in failure to suppress certain pho85 mutant phenotypes. Alternatively, the affinity of Cdk5 for certain Pho85-cyclins may not be strong enough to form a complex of full activity, and/or complexes of Cdk5 and Pho85-cyclins may exhibit altered or loosened substrate specificity compared with that exerted by a combination of Pho85-cyclins and its native kinase. Either of these could result in weak kinase activity unable to phosphorylate appropriate substrates to a sufficient level. This idea can explain why Cdk5 failed to suppress growth arrest of a cln1 cln2 pho85 mutant (Fig. 1). We previously demonstrated that Pcl1-Pho85 can phosphorylate Sic1, targeting it to degradation, which is a major role of Pho85 kinase in the absence of Cln1, 2-Cdc28 kinase activity for cells to proceed through G₁ (19). Although Cdk5 could associate with Pcl1, it failed to phosphorylate Sic1 to a detectable level (Fig. 4, A and B). This idea can also be applied to the argument why Cdk5 that could phosphorylate Pho4 failed to suppress constitutive expression of PHO5 (Fig. 1). Phosphorylation of Pho4 regulates both its export from and import into the nucleus (32, 33), and a recent report demonstrated that the phosphorylation status affects the efficiency of translocation of the transcription factor (34). We imagine that phosphorylation of Pho4 by Cdk5 may decrease the level of the transcription factor in the nucleus sufficient to inactivate transcription of genes responsible for the growth arrest but not to the level enough to repress PHO5 expression. In other words, Pho4-responsive genes may have a different threshold of the transcription factor in the nucleus.

Since the discovery that yeast Cdc28 kinase is a functional homologue of mammalian Cdc2 and other Cdks functioning in the cell cycle, the yeast system has been providing a convenient tool to study the regulation mechanism of the cell cycle. In this paper, we demonstrated that the mammalian Cdk family has another functional homologue of the yeast Cdks. This discovery will lead to further understanding of the function of Cdk5 and Pho85 kinases. The yeast system will provide a tool to identify yet unknown factors that associate with p35-Cdk5 to regulate events involved in neuronal developments. Conversely, Cdk5 kinase can be used to search for yeast proteins interacting with cyclin-Pho85 complex to regulate cell-cycle progression and cell morphology. These studies will provide more insights into regulatory mechanisms of Cdks functioning in the events both related and unrelated to the cell cycle.

	ACKNOWLEDGEMENTS

We thank G. Patrick and H.-L. Tsai, for mouse Cdk5 cDNA clone and Cdk5 monoclonal antibody, and M. Tanabe, for technical assistance.

	FOOTNOTES

^* This work was supported by grant-in-aids for scientific research from Monbu-sho of Japan (to M. N., and A. T.) and by Research Grants for Life Sciences and Medicine from the Keio University Medical Science Fund (to M. N.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^§ To whom correspondence should be addressed: Dept. of Microbiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan. Tel.: 81-3-3353-1211, ext. 62695; Fax: 81-3-5360-1508; E-mail: mas@mc.med.keio.ac.jp.

² Nishizawa, M., Suzuki, K., Fujino, M., Oguchi, T., and Toh-e, A. (1999) Genes Cells, in press.

³ L.-H. Tsai, personal communication.

	ABBREVIATIONS

The abbreviations used are: Cdk, cyclin-dependent kinase; GST, glutathione S-transferase; HA, hemagglutinin; Ab, antibody.

	REFERENCES

TOP ABSTRACT INTRODUCTION EXPERIMENTAL PROCEDURES RESULTS AND DISCUSSION REFERENCES

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				S. Aviram, E. Simon, T. Gildor, F. Glaser, and D. Kornitzer Autophosphorylation-Induced Degradation of the Pho85 Cyclin Pcl5 Is Essential for Response to Amino Acid Limitation Mol. Cell. Biol., November 15, 2008; 28(22): 6858 - 6869. [Abstract] [Full Text] [PDF]

				S. Castillo-Lluva, I. Alvarez-Tabares, I. Weber, G. Steinberg, and J. Perez-Martin Sustained cell polarity and virulence in the phytopathogenic fungus Ustilago maydis depends on an essential cyclin-dependent kinase from the Cdk5/Pho85 family J. Cell Sci., May 1, 2007; 120(9): 1584 - 1595. [Abstract] [Full Text] [PDF]

				Y. Horiuchi, A. Asada, S.-i. Hisanaga, A. Toh-e, and M. Nishizawa Identifying novel substrates for mouse Cdk5 kinase using the yeast Saccharomyces cerevisiae Genes Cells, December 1, 2006; 11(12): 1393 - 1404. [Abstract] [Full Text] [PDF]

				G. Ren, P. Vajjhala, J. S. Lee, B. Winsor, and A. L. Munn The BAR Domain Proteins: Molding Membranes in Fission, Fusion, and Phagy Microbiol. Mol. Biol. Rev., March 1, 2006; 70(1): 37 - 120. [Abstract] [Full Text] [PDF]

				T. Gildor, R. Shemer, A. Atir-Lande, and D. Kornitzer Coevolution of Cyclin Pcl5 and Its Substrate Gcn4 Eukaryot. Cell, February 1, 2005; 4(2): 310 - 318. [Abstract] [Full Text] [PDF]

				D. Huang, J. Moffat, and B. Andrews Dissection of a Complex Phenotype by Functional Genomics Reveals Roles for the Yeast Cyclin-Dependent Protein Kinase Pho85 in Stress Adaptation and Cell Integrity Mol. Cell. Biol., July 15, 2002; 22(14): 5076 - 5088. [Abstract] [Full Text] [PDF]

				D. S. Smith, P. L. Greer, and L.-H. Tsai Cdk5 on the Brain Cell Growth Differ., June 1, 2001; 12(6): 277 - 283. [Abstract] [Full Text] [PDF]

				M. E. Lenburg and E. K. O'Shea Genetic Evidence for a Morphogenetic Function of the Saccharomyces cerevisiae Pho85 Cyclin-Dependent Kinase Genetics, January 1, 2001; 157(1): 39 - 51. [Abstract] [Full Text]

				S. R. Floyd, E. B. Porro, V. I. Slepnev, G.-C. Ochoa, L.-H. Tsai, and P. De Camilli Amphiphysin 1 Binds the Cyclin-dependent Kinase (cdk) 5 Regulatory Subunit p35 and Is Phosphorylated by cdk5 and cdc2 J. Biol. Chem., March 9, 2001; 276(11): 8104 - 8110. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nishizawa, M. Articles by Toh-e, A. Search for Related Content PubMed PubMed Citation Articles by Nishizawa, M. Articles by Toh-e, A. Social Bookmarking                      What's this?