Psychiatry related information on CDC2

• Both cdc2 and MAP2 kinases are present in brain extracts obtained from Alzheimer's disease patients [1].

High impact information on CDC2

• Remarkably, full phosphorylation of all these cdk sites was required for repression of PAP activity, and partial phosphorylation had no detectable effect [2].
• We discuss the possibility that this reflects a general means to control the timing of cdk-dependent regulatory events during the cell cycle [2].
• We propose that PAP's multiple cdk sites, and their differential sensitivity to MPF, provide a mechanism to link repression specifically to late M-phase [2].
• Cell fractionation experiments and in vitro phosphorylation assays demonstrate that the p58 kinase resides in the nuclear envelope and is distinct from protein kinase A and cdc2 kinase, for both of which p58 is an in vitro substrate [3].
• The resulting inhibition of cyclin-dependent kinase and hypophosphorylation of retinoblastoma protein lead to endothelial cell cycle arrest [4].

Biological context of CDC2

• Phosphorylation of neurofilament H subunit at the tail domain by CDC2 kinase dissociates the association to microtubules [5].
• Cyclin B, a positive regulatory subunit of the cdc2 protein kinase complex, is synthesized across the cell cycle and then rapidly degraded at the end of mitosis [6].
• Degradation of cyclin B is triggered by increased levels of active cdc2 and is required for exit from mitosis [6].
• Incubation of the particulate fraction from interphase cells with the protein kinase cdc2 activates it for cyclin-ubiquitin ligation, after a lag of about 30 min [6].
• Western blot analysis and immunocytochemical protein detection combined with multiparameter flow cytometry further demonstrate that the perturbed progression through S and G2 phases is accompanied by an increase in the expression of tumor suppressor gene protein p53 and elevation of the level of cyclin-dependent kinase inhibitor p21(WAF1/CIP1) [7].

Anatomical context of CDC2

• Interplay between CDC2 kinase and MAP kinase pathway during maturation of mammalian oocytes [8].
• The results suggest that this thymus kinase is a novel Cdk inhibitory protein kinase, distinct from the recently cloned dual functional and membrane-associated Cdc2 inhibitory kinase, Myt1 (Mueller, P. R., Coleman, T. R., Kumagai, A., and Durphy, W. G. (1995) Science 270, 86-90) [9].
• HeLa cell p34cdc2 kinase displays similar specificity to that of the bovine cdc2-like kinase, as the additional determinants outside of the consensus motif that contribute to the efficient phosphorylation of the histone peptide by this novel enzyme also appear to be important for p34cdc2-catalyzed phosphorylation [10].
• Prolonged cell-cycle arrest associated with altered cdc2 kinase in monocrotaline pyrrole-treated pulmonary artery endothelial cells [11].
• Co-culture with pig membrana granulosa cells modulates the activity of cdc2 and MAP kinase in maturing cattle oocytes [12].

Associations of CDC2 with chemical compounds

• Using cdc2 kinase, 7-10 mol of phosphoryl groups was incorporated per mole of MAP2, and more than 60% of the phosphates was distributed to the microtubule-binding region [13].
• Poly(A) RNA is reduced by half during bovine oocyte maturation but increases when meiotic arrest is maintained with CDK inhibitors [14].
• Roscovitine reversibly prevented this drop in relative quantities of CDK1 messenger [15].
• 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 [16].
• Demonstration of cyclin-dependent kinase inhibitory serine/threonine kinase in bovine thymus [9].

Physical interactions of CDC2

• These observations show that cdc2 kinase-dependent phosphorylation inhibits both the microtubule-stabilizing activity and the microtubule-nucleating activity of MAP2, while PKA-dependent phosphorylation affects only the microtubule-nucleating activity of MAP2 [13].

Enzymatic interactions of CDC2

• In cdc2 kinase-phosphorylated MAP2, however, the phase transition from depolymerization to polymerization occurred with difficulty, with the result being that the half-life of individual microtubules was as short as in the absence of MAP2 [13].

Other interactions of CDC2

• Identification of cDNAs encoding bovine cyclin B and Cdk1/Cdc2 [17].
• Components of a system that ligates cyclin to ubiquitin and their regulation by the protein kinase cdc2 [6].
• Examination of spontaneous polymerization of microtubules using dark-field microscopy showed that the microtubule-nucleating activity of MAP2 was reduced by PKA-dependent phosphorylation and was completely abolished by cdc2 kinase-dependent phosphorylation [13].
• Apoptosis of EC mediated by TGF-beta1 was associated with a decreased level of the cyclin-dependent kinase inhibitor p21waf1/cip1, compared with that observed in the apoptosis-resistant cells [18].
• Treatment with 80 microg/ml EGCG induced the tumor suppressor p53, which was functional as judged by activation of the target cyclin-dependent kinase inhibitor p21CIP1 [19].

Analytical, diagnostic and therapeutic context of CDC2

• In contrast, A23187+6-DMAP treatment resulted in earlier phosphorylation of cdc2 and dephosphorylation of ERK2 at 4 h after treatment when the pronucleus formed [20].
• Western blot examination revealed that by 24 h of MCTP exposure, the phosphorylation state of cdc2 was consistent with the inactive form of the kinase (confirmed by biochemical assay); this alteration persisted through at least 96 h of exposure [11].
• Tau, phosphorylated by neuronal cdc2-like kinase, associated with DNA as shown by electrophoretic mobility shift assay [21].

References