Protein cdc2, phosphorylation

Lees, J.A., K.J. Buchkovich, D.R. Marshak, C.W. Anderson E. Harlow. 1991. The retinoblastoma protein is phosphorylated on multiple sites by human cdc2. EMBO J. 10 4279-90. 

In parallel, the cell cycle progression was also explored with the breast tumor cell line MCF-7. Attention was focused on the evolution of P21 and cycfin Dl two proteins acting as regulators during the cell cycle progression (G1 phase or growth phase) and the phosphorylation of the protein cdc2 (indicator of G2... 

Draetta, G., and Beach, D. (1988). Activation of cdc2 protein kinase during mitosis in human cells cell cycle-dependent phosphorylation and subunit rearrangement. Cell 54 17-24. 

Gould, K. L., and Nurse, P. (1989). Tyrosine phosphorylation of the fission yeast cdc2+ protein kinase regulates entry into mitosis. Nature 342 39-45. 

Pickham, K. M., Meyer, A. N., Li, J and Donoghue, D. J. (1992). Requirement of mosx protein kinase for meiotic maturation of Xenopus oocytes induced by a cdc2 mutant lacking regulatory phosphorylation sites. Mol. Cell. Biol. 12 3192-3203. 

Simanis, V., and Nurse, R (1986). The cell cycle control gene cdc2+ of fission yeast encodes a protein kinase potentially regulated by phosphorylation. Cell 45 261-268. 

Phosphorylation of HI during mitosis is catalyzed by the cyclin B-Cdc2 kinase, a tightly regulated enzyme [25,26]. In Tetrahymena mitotically dividing nuclei, cyclic-AMP dependent kinase (PKA) or PKA-like kinase phosphorylates HI [27,28]. Protein phosphatase 1 dephosphorylates the phosphorylated HI [29]. 

Entry of animal cells into mitosis is based on the mitosis-promoting factor (MPF). MPF consists of CDK1 (cdc2) and cyclin B. The intracellular concentration of cyclin B increases constantly until mitosis starts, and then declines again rapidly (top left). MPF is initially inactive, because CDKl is phosphorylated and cyclin B is dephosphorylated (top center). The M phase is triggered when a protein phosphatase [1] dephosphorylates the CDK while cyclin B is phosphorylated by a kinase [2]. in its active form, MPF phosphorylates various proteins that have functions in mitosis—e.g., histone HI (see p. 238), components of the cytoskeleton such as the laminins in the nuclear membrane, transcription factors, mitotic spindle proteins, and various enzymes. 

Phosphorylation of the CycA-CDC2 complex at ThrlhO leads to a near 300-fold increase in protein kinase activity. Thrl60 of CDK2 hes in the activation segment (also known as the T loop) that blocks the access to the substrate binding site in the inactive... 

The inactivating phosphorylation at Thrl4 and TyrlS can be reversed by specific phosphatases in a regulated marmer. The dephosphorylation is performed by CDC2S phosphatase. This enzyme, first described for S. pombe, is a protein phosphatase with twofold specificity that can cleave phosphate residues from phosphoserine and phosphoty-rosine residues of CDKs. CDC2S phosphatases have also been observed in higher eucaryotes where they have a similar fimction. 

In M phase, new phosphorylation of many proteins is observed that starts, in particular, from the CDC2-cyclin B complex. The phosphorylation mostly affects proteins involved in the reorganization of the cytoskeleton, the nuclear membrane and the formation of the spindle apparatus. As a consequence of phosphorylation events, inhibition of vesicular transport and general inhibition of transcription occur. 

Feuerstein, N. Phosphorylation of numatrin and other nuclear proteins by cdc2 containing CTD kinase cdc2/p58. J. Biol. Chem., 266, 16200-16206 (1991)... 

To determine the effect of circadian rhythms on anticancer drug administration, it is important to incorporate the link between the circadian clock and the cell cycle. Entrainment by the circadian clock can be included in the automaton model by considering that the protein Weel undergoes circadian variation, because the circadian clock proteins CLOCK and BMAL1 induce the expression of the Weel gene (see Fig. 10.1b) [3-5]. Weel is a kinase that phosphorylates and thereby inactivates the protein kinase cdc2 (also known as the cyclin-dependent kinase Cdkl) that controls the transition G2/M and, consequently, the onset of mitosis. 

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