Cyclin phosphorylation

Clurman, B. E., Sheaff, R. J., Thress, K., Groudine, M., and Roberts, J. M. (1996). Turnover of cyclin E by the ubiquitin-proteasome pathway is regulated by cdk2 binding and cyclin phosphorylation. Genes Dev 10, 1979-1990. 

The activity of a cyclin-CDK complex changes during the cell cycle through differential synthesis of CDKs, specific degradation of cyclin, phosphorylation and dephosphorylation of critical residues in CDKs, and binding of inhibitory proteins to specific cyclin-CDICs. 

Signal-directed phosphorylation of cyclins is a tool for targeting cyclins for proteolysis. Furthermore, cyclin phosphorylation influences the subcellular distribution of cyclins. 

In free CDK2 the active site cleft is blocked by the T-loop and Thr 160 is buried (Figure 6.20a). Substrates cannot bind and Thr 160 cannot be phosphorylated consequently free CDK2 is inactive. The conformational changes induced by cyclin A binding not only expose the active site cleft so that ATP and protein substrates can bind but also rearrange essential active site residues to make the enzyme catalytically competent (Figure 6.20b). In addition Thr... 

Figure 13.30 Ribbon diagram of the structure of Src tyrosine kinase. The structure is divided in three units starting from the N-terminus an SH3 domain (green), an SH2 domain (blue), and a tyrosine kinase (orange) that is divided into two domains and has the same fold as the cyclin dependent kinase described in Chapter 6 (see Figure 6.16a). The linker region (red) between SH2 and the kinase is bound to SH3 in a polyproline helical conformation. A tyrosine residue in the carboxy tail of the kinase is phosphorylated and bound to SH2 in its phosphotyrosine-binding site. A disordered part of the activation segment in the kinase is dashed. (Adapted from W. Xu et al.. Nature 385 595-602, 1997.)...

Cell Cycle Control. Figure 1 Cell cycle regulation by Cyclin dependent kinases (CDKs). Different cyclins bound to different CDKs promote the transition from one cell cycle phase into another. CDK-dependent phosphorylation of Rb is required to release active E2F transcription factors, which promotes entry into S phase. 

Izumi, T., and Mailer, J. L. (1991). Phosphorylation of Xenopus cyclins B1 andB2is not required for cell cycle transitions. Mol. Cell. Biol. 11 3860-3867. 

The biochemical mechanism of Mos action is not yet established. Mos has been found to phosphorylate cyclin B in vitro, and it is possible that this phosphorylation directly inhibits cyclin B proteolysis (Roy et al., 1990). However, such a direct effect of phosphorylation on cyclin B stability remains to be demonstrated, and it is alternatively possible that Mos inhibits (directly or indirectly) the proteolytic pathway responsible for cyclin B degradation. Mos has recently been found to stimulate mitogen-activated protein kinase (MAP kinase) in Xenopus oocytes,... 

Mailer There are some stories coming out that Weel comes up in meiosis II. There might be low HI kinase activity, but there is still cyclin B present in a tyrosine-phosphorylated Cdc2 complex, and this might or might not be able to signal something about cell cycle phase. 

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