p40MO15, a cdc2-related protein kinase involved in negative regulation of meiotic maturation of Xenopus oocytes.

Shuttleworth, James; Godfrey, Rita E.; Colman, Alan

doi:10.1002/j.1460-2075.1990.tb07522.x

Cited by 99 publications

(76 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Taken together with the seminal observation that M015 mRNA is, by virtue of alternative start sites (Shuttleworth et al, 1990), capable of yielding two different forms of the kinase, these findings raise the possibility that structurally and functionally distinct isoforms of Cak1 may participate in transcriptional regulation vis à vis cell cycle control pathways. Alternatively, the association of Cak1 with multiple regulatory subunits (i.e.…”

Section: Cak1mentioning

confidence: 74%

“…Comparatively high levels of p42 cak1 were detected in rat and human osteosarcoma cells (Fig. 1C), both of which exhibited additional immunoreactive protein band(s) at ϳ44 and ϳ55 kDa, possibly representing alternatively spliced or closely related isoforms of the Cak1 kinase (see Shuttleworth et al (1990)). …”

Section: Characterization and Application Of Specific Anti-cak1mentioning

confidence: 98%

“…B, titration of Cak1 detection upon Western blotting by polyclonal anti-Cak1 antibodies raised against the immunizing peptide. Note comparative cross-reactivity with Xenopus M015, which exhibits a similar but nonidentical C terminus (see Shuttleworth et al, 1990)…”

Section: Characterization and Application Of Specific Anti-cak1mentioning

confidence: 99%

“…Our previous studies of Cdc2 phosphorylation led to the isolation (Williams et al, 1993a(Williams et al, , 1993b) and molecular cloning of the human Cdk-activating kinase, p42 cak1 , a homologue of Xenopus MO15 (Shuttleworth et al, 1990) that targets the phosphoregulatory sites within subdomain VIII of Cdc2 and Cdk2 (Solomon, 1993(Solomon, , 1994Solomon et al, 1993;Poon et al, 1993). The striking (Molz and Beach, 1993), the human cyclin H , and human cyclin C .…”

Section: Cdk2mentioning

confidence: 99%

“…An essential phosphoregulatory site, deduced from genetic studies in yeast, was identified within the T-fold of kinase subdomain VIII (Marcote et al, 1993;DeBondt et al, 1993) of Cdc2 (at and Cdk2 (at Thr-160) and whose phosphorylation is required for the generation of Cdc2/Cdk2 kinase activity (Krek et al, 1992;Gu et al, 1992;Connell-Crowley et al, 1993). Subsequent studies have identified a distinctive Cdc2/Cdk2-activating protein kinase (CAK) in Xenopus oocytes, MO15 (Shuttleworth et al, 1990;Poon et al, 1993;Solomon et al, 1993), and human tumor cells Williams et al, 1993aWilliams et al, , 1993b. The catalytic subunit of the human CAK (Cak1) has been cloned and is found to be structurally related to Cdc2(Hs) .…”

mentioning

confidence: 99%

See 4 more Smart Citations

Biochemical Characterization of the Human Cyclin-dependent Protein Kinase Activating Kinase

Yee

Liu

et al. 1996

Journal of Biological Chemistry

View full text Add to dashboard Cite

The activation of cyclin-dependent protein kinases (Cdks) is dependent upon site-specific phosphorylation and dephosphorylation reactions, as well as positive and negative regulatory subunits. The human Cdk-activating protein kinase (Cak1) is itself a Cdc2-related cyclin-dependent protein kinase that associates with cyclin H. The present study utilized specific anti-Cak1 antibodies and immunoaffinity chromatography to identify additional Cak1-associated proteins and potential target substrates. Immunoprecipitation of metabolically labeled human osteosarcoma cells revealed a number of Cak1-associated proteins, including p95, p37 (cyclin H), and a 35-kDa protein that was further characterized herein. Microsequence analysis obtained after limited proteolysis revealed peptide fragments that are similar, but not identical to, human and yeast cyclins, thus identifying p35 as a cyclin-like regulatory subunit. The greatest sequence similarity of human p35 is with Mcs2, a yeast cyclin that is essential for cell cycle progression. Immunoaffinity chromatography performed under nondenaturing conditions afforded the isolation of enzymatically active Cak1 from cell lysates, enabling studies of kinase autophosphorylation and comparative substrate utilization. Immunoaffinity-purified Cak1 phosphorylated monomeric Cdc2 and Cdk2, but not Cdk4; the phosphorylation of both Cdc2 and Cdk2 were increased in the presence of recombinant cyclin A. These studies indicate that the Cak1 catalytic subunit, like Cdc2 and Cdk2, associates with multiple regulatory partners and suggests that subunit composition may be an important determinant of this multifunctional enzyme.

show abstract

Section: Cak1mentioning

confidence: 74%

Section: Characterization and Application Of Specific Anti-cak1mentioning

confidence: 98%

Section: Characterization and Application Of Specific Anti-cak1mentioning

confidence: 99%

Section: Cdk2mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Biochemical Characterization of the Human Cyclin-dependent Protein Kinase Activating Kinase

Yee

Liu

et al. 1996

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

Expression of CDK7/CAK in normal and tumour cells of diverse histogenesis, cell-cycle position and differentiation

1996

View full text Add to dashboard Cite

The cyclin-dependent kinase 7 (CDK7) represents the 40-kDa catalytic subunit of the CDK-activating kinase, the enzyme responsible for activatory phosphorylation of multiple CDKs controlling GI, S and G2/M phases of the cell cycle. Here, we surveyed a wide range of normal and tumour cell types, in both cell culture and biopsy specimens, for abundance and subcellular localisation of the CDK7 protein. lmmunoblotting and immunocytochemical analyses showed that CDK7 was (i) ubiquitously expressed in all cell types examined; (ii) exclusively nuclear: (iii) moderately elevated in turnour cells when compared with their normal cell counterparts; (iv) invariant throughout the cell cycle of normal lymphocytes, fibroblasts, breast epithelium and several cancer cell lines; and (v) clearly detectable even in quiescent cells, including highly differentiated cell types in situ. Our data are consistent with the emerging role for CDK7/CAK in multiple biological processes, possibly providing a link between cell-cycle control, transcriptional regulation and genomic integrity control.o 1996 Wiley-Liss, Inc.Transitions through the ordered checkpoints that control the mammalian cell cycle are triggered by activation of a distinct class of serine/threonine kinases, the cyclin-dependent kinases (CDKs). To ensure proper timing and mutual coordination of the major cell-cycle events, the CDKs are carefully regulated by multiple mechanisms (Clarke, 1995;Doree and Galas, 1994;Morgan, 1995;Sherr and Roberts, 1995). One such mechanism is an activatory phosphorylation of a conserved threonine residue (Thr 160 in CDK2, Thr 161 in CDC2 and their equivalents in other CDKs) within the T loop of various CDKs (Clarke, 1995;Doree and Galas, 1994;Morgan, 1995). This phosphorylation appears to alter conformation of the T loop, to stabilize the CDK-cyclin interaction and probably to render the catalytic domain of CDKs accessible to their cellular protein substrates Pines, 1995). A kinase responsible for phosphorylating the threonine residue has been identified in various organisms and designated CAK, for CDK-activating kinase (Darbon et al., 1994; Fesquet etal., 1993 (Shuttleworth et al., 1990). The catalytic subunit of CAK itself, therefore, appears to be a member of the CDK family, and it requires binding to a regulatory cyclin subunit to become active (Clarke, 1995;Fisher and Morgan, 1994;Makela et al., 1994;Morgan, 1995). The CAK has therefore been recently renamed CDK7 and its novel cyclin partner termed cyclin H Makela et al., 1994).Accumulating evidence implicates deregulation of some of the components of the mammalian cell-cycle machinery in oncogenesis. In particular, over-expression of D-type cyclins or their CDK4 partner kinase appears to be involved in pathogenesis of several human cancer types, and these positive cell cycle regulators qualify as new proto-oncogenes (Bartkova et al., 19956;Hunter and Pines, 1994;Sherr and Roberts, 1995;Strauss et al., 1995). Since CDK7/CAK activates the key CDKs at various cell-cycle transitions, including...

show abstract

On cyclins, oocytes, and eggs

1997

View full text Add to dashboard Cite

Oocyte and egg are suitable model systems for studying cell division since meiotic maturation resembles a G2/M transition and early embryonic divisions are precisely timed and occur without zygotic transcription. The analysis of oocytes and eggs from different species provides the opportunity to understand the roles of proteins that are critical to the progression and maintenance of the cell cycle. Among them, cyclins are certainly worthy of investigation. Mitotic cyclins (cyclins A and B) are clearly implicated in meiosis and early embryonic cell cycles. More recent studies have revealed that G1‐type cyclins (cyclins E and D) could also play a role in both processes and cyclin H has been suggested to participate to CAK activity (cdc2‐activating kinase) in oocytes. The study of cyclins in oocytes and eggs clearly offer insights into their roles during the cell cycle. Mol. Reprod. Dev. 48:397–411, 1997. © 1997 Wiley‐Liss, Inc.

show abstract

p40MO15, a cdc2-related protein kinase involved in negative regulation of meiotic maturation of Xenopus oocytes.

Cited by 99 publications

References 62 publications

Biochemical Characterization of the Human Cyclin-dependent Protein Kinase Activating Kinase

Biochemical Characterization of the Human Cyclin-dependent Protein Kinase Activating Kinase

Expression of CDK7/CAK in normal and tumour cells of diverse histogenesis, cell-cycle position and differentiation

On cyclins, oocytes, and eggs

Contact Info

Product

Resources

About