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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bud emergence, spindle pole body duplication and DNA replication are all dependent on the activation of the CDC28 protein kinase at the Start point in the G1 phase of the cell cycle. Bud emergence requires polarization of the cytoskeleton and secretory vesicles to a specific site on the cell surface. Cdc28p activated by G1-cyclins triggers polarization of actin to the site of bud emergence and favors apical bud growth (Lew, D. J., and S. I. Reed. 1993. J. Cell Biol. 120:1305-1320). We isolated slt2-1 as a mutation that enhances the division defect of cdc28 mutants with defects at Start. Slt2p(Mpk1p) is a member of the MAP kinase family (Lee, K. S., K. Irie, Y. Gotoh, Y. Watanabe, H. Araki, E. Nishida, K. Matsumoto, and D. E. Levin. 1993. Mol. Cell. Biol. 13:3067-3075). We show that slt2 mutants exhibit phenotypes similar to those shown by mutants of the yeast actin cytoskeleton, including delocalization of chitin deposition and of actin cortical spots and the accumulation of secretory pathway membranes and vesicles. Furthermore, slt2::HIS3 act1-1 and slt2::HIS3 myo2-66 double mutants are inviable. We suggest that Slt2p functions downstream or in parallel with Cdc28p in promoting bud formation and apical growth.
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PMID:The SLT2 (MPK1) MAP kinase homolog is involved in polarized cell growth in Saccharomyces cerevisiae. 827

beta gamma subunits of G proteins were purified from starfish oocytes, and their role in the induction of oocyte maturation by 1-methyladenine was investigated. When injected into starfish oocytes, the purified beta gamma subunit of the starfish G protein induced germinal vesicle breakdown (GVBD) faster than that of bovine brain G protein. Injection of the starfish beta gamma into cytoplasm near the germinal vesicle (GV) induced GVBD earlier than when injected into the GV or the cytoplasm near the plasma membrane. Fluorescent-labeled beta gamma was retained in the injected area even after GVBD. Injected beta gamma also induced the formation of maturation-promoting factor as well as an increase of histone H1 kinase activity. These results suggest that beta gamma dissociates from alpha-subunit by the stimulation of 1-methyladenine and interacts with a cytoplasmic effector, which results in formation of active cdc2 kinase.
Mol Biol Cell 1993 Oct
PMID:Induction of starfish oocyte maturation by the beta gamma subunit of starfish G protein and possible existence of the subsequent effector in cytoplasm. 829 89

The transcription factor E2F activates the expression of multiple genes involved in cell proliferation, such as c-myc and the dihydrofolate reductase gene. Regulation of E2F involves its interactions with other cellular proteins, including the retinoblastoma protein (Rb), the Rb-related protein p107, cyclin A, and cdk2. We undertook a detailed analysis of E2F DNA-binding activities and their cell cycle behavior in primary human T cells. Three E2F DNA-binding activities were identified in resting (G0) T cells with mobilities in gel shift assays distinct from those of previously defined E2F complexes. One of these activities was found to be a novel, less abundant, Rb-E2F complex. The most prominent E2F activity in resting T cells (termed complex X) was abundant in both G0 and G1 but disappeared as cells entered S phase, suggesting a possible role in negatively regulating E2F function. Complex X could be dissociated by adenovirus E1A with a requirement for an intact E1A conserved region 2. However, X failed to react with a variety of antibodies against Rb or p107, implicating the involvement of an E1A-binding protein other than Rb or p107. In addition to these novel E2F complexes, three distinct forms of unbound (free) E2F were resolved in gel shift experiments. These species showed different cell cycle kinetics. UV cross-linking experiments suggested that a distinct E2F DNA-binding protein is uniquely associated with the S-phase p107 complex and is not associated with Rb. Together, these results suggest that E2F consists of multiple, biochemically distinct DNA-binding proteins which function at different points in the cell cycle.
Mol Cell Biol 1993 Jul
PMID:Cell cycle analysis of E2F in primary human T cells reveals novel E2F complexes and biochemically distinct forms of free E2F. 832 Dec 4

The mak gene encodes a new protein kinase distantly related to cdc2 kinase, and its transcripts are expressed exclusively in testicular germ cells at and after meiosis (H. Matsushime, A. Jinno, N. Takagi, and M. Shibuya, Mol. Cell. Biol. 10:2261-2268, 1990). In this study, we prepared a series of antibodies against synthetic peptides and fusion products of the mak gene and characterized the subcellular localization, protein kinase activity, and association with other cellular proteins of Mak. Mak products were identified as 66- and 60-kDa proteins that specifically appeared in rat testes after puberty. Testicular germ cell fractionation revealed that Mak products were most abundant in the fraction of the late pachytene stage and that their levels were dramatically decreased in postmeiotic haploid cells. Mak products were localized mostly in the cytoplasm as a soluble form. [35S]methionine labelling demonstrated that Mak products were associated with a 210-kDa cellular protein; in an in vitro kinase assay with immunoprecipitates of Mak products, the 210-kDa cellular protein was efficiently phosphorylated on serine and threonine residues. Furthermore, in a testicular cell culture system with 32Pi, the 210-kDa molecule associated with Mak was phosphorylated in vivo on serine and threonine residues. These results strongly suggest that the Mak complex may play a role in meiosis during spermatogenesis and that a phosphorylated 210-kDa protein is one of the physiological substrates for this protein kinase.
Mol Cell Biol 1993 Jul
PMID:Testis-specific mak protein kinase is expressed specifically in the meiotic phase in spermatogenesis and is associated with a 210-kilodalton cellular phosphoprotein. 832 Dec 19

Receptor-mediated endocytosis and recycling are inhibited in mitotic mammalian cells, and previous studies have shown that inhibition of endocytic vesicle fusion in vitro occurs via cyclin B-cdc2 kinase. To test for the ability of cyclin A-cdc2 kinase to inhibit endocytic vesicle fusion, we employed recombinant cyclin A proteins. Addition of cyclin A to interphase extracts activated a histone kinase and markedly reduced the efficiency of endocytic vesicle fusion. By a number of criteria, inhibition of fusion was shown to be due to the action of cyclin A, via the mitosis-specific cdc2 kinase, and not an indirect effect through cyclin B. Two-stage incubations were used to demonstrate that at least one target of cyclin A-cdc2 kinase is a cytosolic component of the fusion apparatus. Reconstitution experiments showed that this component was also modified in mitotic cytosols and was unaffected by N-ethyl maleimide treatment.
Mol Biol Cell 1993 May
PMID:In vitro fusion of endocytic vesicles is inhibited by cyclin A-cdc2 kinase. 833 8

The yeast Cdc7 function is required for the G1/S transition and is dependent on passage through START, a point controlled by the Cdc28/cdc2/p34 protein kinase. CDC7 encodes a protein kinase activity, and we now show that this kinase activity varies in the cell cycle but that protein levels appear to remain constant. We present several lines of evidence that periodic activation of CDC7 kinase is at least in part through phosphorylation. First, the kinase activity of the Cdc7 protein is destroyed by dephosphorylation of the protein in vitro with phosphatase. Second, Cdc7 protein is hypophosphorylated and inactive as a kinase in extracts of cells arrested at START but becomes active and maximally phosphorylated subsequent to passage through START. The phosphorylation pattern of Cdc7 protein is complex. Phosphopeptide mapping reveals four phosphopeptides in Cdc7 prepared from asynchronous yeast cells. Both autophosphorylation and phosphorylation in trans appear to contribute to this pattern. Autophosphorylation is shown to occur by using a thermolabile Cdc7 protein. A protein in yeast extracts can phosphorylate and activate Cdc7 protein made in Escherichia coli, and phosphorylation is thermolabile in cdc28 mutant extracts. Cdc7 protein carrying a serine to alanine change in the consensus recognition site for Cdc28 kinase shows an altered phosphopeptide map, suggesting that this site is important in determining the overall Cdc7 phosphorylation pattern.
Mol Biol Cell 1993 Feb
PMID:Regulation of Saccharomyces cerevisiae CDC7 function during the cell cycle. 838 76

The cdc2 kinases are important cell cycle regulators in all eukaryotes. MAP kinases, a closely related family of protein kinases, are involved in cell cycle regulation in yeasts and vertebrates, but previously have not been documented in plants. We used PCR to amplify Brassica napus DNA sequences using primers corresponding to amino sequences that are common to all known protein kinases. One sequence was highly similar to KSS1, a MAP kinase from Saccharomyces cerevisiae. This sequence was used to isolate a full-length MAP kinase-like clone from a pea cDNA library. The pea clone, called D5, shared approximately 50% amino acid identity with MAP kinases from yeasts and vertebrates and about 41% identity with plant cdc2 kinases. An expression protein encoded by D5 was recognized by an antiserum specific to human MAP kinases (ERKs). Messenger RNA corresponding to D5 was present at similar levels in all tissues examined, without regard to whether cell division or elongation were occurring in those tissues.
Plant Mol Biol 1993 Apr
PMID:Molecular cloning and expression of a MAP kinase homologue from pea. 838 49

The transcription factor E2F has been shown to be involved in the expression of several cell cycle-regulated genes, and the activity of this factor is controlled by cellular proteins such as pRB and p107. E2F is also a target of the DNA virus oncoproteins (adenovirus E1A, simian virus 40 T antigen, and human papillomavirus [HPV] E7) (see the review by J. R. Nevins [Science 258: 424-429, 1992]). These viral oncoproteins dissociate an inactive complex between E2F and the retinoblastoma tumor suppressor protein (pRB), and this dissociation of the E2F-pRB complex correlates with a stimulation of the E2F-dependent transcription. In the S phase of the cell cycle, E2F forms a complex with p107, cyclin A, and the cdk2 kinase (E2F-cyclin A complex). The cellular function of this S-phase-specific complex is unclear. The adenovirus E1A protein dissociates the E2F-cyclin A complex. The HPV type 16 (HPV-16) E7 protein, which possesses significant sequence homology with E1A, does not dissociate the E2F-cyclin A complex. We find that the HPV-16 E7 protein associates very efficiently with the E2F-cyclin A complex. This association is dependent on the sequences that are also necessary for the transforming activity of E7. Moreover, the E7 protein of a low-risk HPV (type 6b) is much less efficient in binding to the E2F-cyclin A complex compared with that of the high-risk type. We also find that the E2F-cyclin A complex remains endogenously associated with the E7 protein in extracts of Caski cells, which express high levels of HPV-16 E7 protein. Finally, we have extensively purified the E2F-cyclin A complex from mouse L-cell extracts and show that, in cell extracts, the E2F-cyclin A complex remains associated with other cellular proteins.
Mol Cell Biol 1993 Oct
PMID:Association of the human papillomavirus type 16 E7 protein with the S-phase-specific E2F-cyclin A complex. 841 52

The adenovirus E1A protein can disrupt protein complexes containing the E2F transcription factor in association with cellular regulatory proteins such as the retinoblastoma gene product (Rb) and the Rb-related p107 protein. Previous experiments have shown that the CR1 and CR2 domains of E1A are required for this activity. We now demonstrate that the CR2 domain is essential for allowing E1A to interact with the E2F-Rb or the E2F-p107-cyclin A-cdk2 complex. Multimeric complexes containing E1A can be detected when the CR1 domain has been rendered inactive by mutation. In addition, the E1A CR1 domain, but not the CR2 domain, is sufficient to prevent the interaction of E2F with Rb or p107. On the basis of these results, we suggest a model whereby the CR2 domain brings E1A to the E2F complexes and then, upon a normal equilibrium dissociation of Rb or p107 from E2F, the E1A CR1 domain is able to block the site of interaction on Rb or p107, thereby preventing the re-formation of the complexes.
Mol Cell Biol 1993 Nov
PMID:Identification of distinct roles for separate E1A domains in disruption of E2F complexes. 841 92

Cyclins are pivotal in the coordinate regulation of the cell cycle. By physical association, they are able to activate at least one of the cyclin-dependent kinases, cdc2. How this association between the catalytic moiety and cyclins leads to subsequent activation of the kinase remains unclear. In this report, we describe experiments to investigate this event at a physical level. Our approach was to map the regions required on the cyclin A molecule for interaction with cdc2. We have mapped the contact regions to two small noncontiguous stretches of amino acids, residues 189 to 241 and 275 to 320, both located within the conserved cyclin box domain of the protein. We have further shown that this region not only represents a contact site for cdc2 but apparently represents an intact functional domain with respect to cdc2 activation. This region alone is sufficient to stimulate maturation when injected into immature Xenopus laevis oocytes. This observation implies that events leading to the activation of cdc2 kinase can be mediated through small regions of the cyclin molecule that are located in the cyclin box. These regions contain some of the most highly conserved residues found between all the cyclin members so far identified. This suggests that the cyclin family members may have conserved a similar mechanism to bind and activate cyclin-dependent kinases.
Mol Cell Biol 1993 Feb
PMID:Sequences within the conserved cyclin box of human cyclin A are sufficient for binding to and activation of cdc2 kinase. 842 86


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