High impact information on CDC2

• These results lead us to propose that mitotic disassembly of the nuclear lamina results from direct phosphorylation of lamins by cdc2 kinase [1].
• Here we show that the cdc2 kinase, a major element implicated in controlling the eukaryotic cell cycle, phosphorylates chicken B-type lamins in vitro on sites that are specifically phosphorylated during M phase in vivo [1].
• Following the identification of the cdc2 kinase as a major element controlling entry of cells into mitosis, it is important to define the physiological target range of this enzyme [2].
• Reduction in Hsp90alpha expression caused instability of a cyclin-dependent kinase, Cdc2, and cell cycle progression was blocked mainly at the G2 phase, but also at G1 phase even at mild heat shock temperatures [3].
• These results highlight an unexpected role for cyclin D as a CDK-independent repressor of transcriptional activation by v-Myb but not c-Myb [4].

Biological context of CDC2

• Moreover, when expressed in fission yeast, the chicken cdc2 kinase is able to rescue a temperature-sensitive (ts) cdc2 mutant, demonstrating that it is functional as a cell cycle regulator [5].
• We have isolated a cDNA clone for the chicken homolog of the cdc2 gene, raised antibodies against the corresponding protein, and studied the expression of cdc2 mRNA and protein during chicken embryonic development [5].
• Our finding supports the model that phosphorylation of caldesmon by cdc2 kinase at mitosis may contribute to the disassembly of the microfilament bundles during prophase [6].
• Terminal differentiation of normal chicken erythroid progenitors: shortening of G1 correlates with loss of D-cyclin/cdk4 expression and altered cell size control [7].
• FKBP12 is reported to be associated with the ryanodine-receptor and IP3 Ca2+ channels, and to regulate cell proliferation via binding transforming growth factor (TGF)-beta receptor and cyclin dependent kinase (CDK) [8].

Anatomical context of CDC2

• The cdc2 protein kinase plays a key role in controlling the eukaryotic cell cycle [5].
• By Northern analysis and immunoblotting, we found that in total embryos both cdc2 mRNA and protein levels decreased substantially between day 3 and day 11 after egg laying, and no significant amounts of either cdc2 mRNA or protein were detected in adult liver, brain, heart or skeletal muscle [5].
• Caldesmon phosphatase was identified in chicken gizzard smooth muscle by using as substrates caldesmon phosphorylated at different sites by protein kinase C, Ca2+/calmodulin-dependent protein kinase II and cdc2 kinase [9].
• Phosphorylation and activation of smooth muscle myosin light chain kinase by MAP kinase and cyclin-dependent kinase-1 [10].

Associations of CDC2 with chemical compounds

• CDC2 can mediate the effects of IGF-II on ovarian P4 secretion but not on other hormones [11].
• Accumulation of PKA and CDC2 and secretion of progesterone (P4), testosterone (T), estradiol (E2) and arginine-vasotocin (AVT) were evaluated by using SDS-PAGE-Western blotting and RIA/EIA [11].
• For this purpose, we studied the influence of an inhibitor of PKA (KT5720; 50 ng/ml), a CDC2 blocker (olomoucine; 1 microg/ml), IGF-II (0, 1, 10 or 100 ng/ml) and their combinations on cultured fragments of chicken ovarian follicular wall [11].
• Surprisingly, dephosphorylation of tyrosine 15 did not accompany Cdc2 activation during premature entry to mitosis in Chk1-/- cells, although mitotic phosphorylation of cyclin B2 did occur [12].
• cdc2 kinase phosphorylation of desmin at three serine/threonine residues in the amino-terminal head domain [13].

Regulatory relationships of CDC2

• The role of protein kinase A and cyclin-dependent (CDC2) kinase in the control of basal and IGF-II-induced proliferation and secretory activity of chicken ovarian cells [11].

Other interactions of CDC2

• In vitro kinase assays demonstrated a corresponding massive activation of the cyclin A-regulated, cyclin-dependent kinase 2 but not of cyclin-dependent kinase 2 protein level in muscle homogenates after 1.5 days of muscle loading [14].

Analytical, diagnostic and therapeutic context of CDC2

• Sequence analysis of purified phosphopeptides derived from cdc2 kinase-phosphorylated desmin revealed that Ser-6, Ser-22 and Thr-64 in the N-terminal head domain were the sites phosphorylated [13].

References