Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.16 (calcineurin)
 17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gradual accumulation of cyclin in the frog egg induces an abrupt and concerted activation of p34cdc2 that initiates mitosis. Activation is delayed even after the accumulation of cyclin to a critical threshold concentration. We have reproduced these unusual kinetic properties of p34cdc2 activation in vitro using bacterially expressed cyclin proteins and extracts derived from Xenopus eggs. Abrupt activation follows a lag period, the length of which is independent of the concentration of cyclin. The threshold concentration of cyclin and the length of the lag period are regulated by INH, an inhibitor of MPF activation in oocytes recently identified as a type 2A protein phosphatase. Binding to cyclin induces both tyrosine and threonine phosphorylation of the previously unphosphorylated p34cdc2, rendering it inactivated. The concerted transition into mitosis involves both a reduction in the rate of p34cdc2 phosphorylation on tyrosine and an increase in its rate of dephosphorylation.
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PMID:Cyclin activation of p34cdc2. 214 72

We have developed a soluble, cell-free system from premeiotic Xenopus oocytes that executes the post-translational activation of a precursor form of maturation promoting factor (MPF). We have distinguished at least two components of this ATP-dependent reaction: pre-MPF, a precursor to MPF that activates independently of added MPF and whose apparent molecular weight changes from 400 kd to 260 kd upon activation; and INH, an inhibitor of pre-MPF activation that confers MPF dependence on the reaction. We present evidence suggesting that INH is a phosphatase and that the activation of pre-MPF occurs via phosphorylation. INH activity itself seems to be regulated by another phosphatase, protein phosphatase-1. We have directly examined the pattern of protein phosphorylation during the activation reaction and have found 92 and 140 kd proteins whose phosphorylation increases when MPF activity appears. This system makes possible a direct examination of the regulation of MPF activity during the cell cycle.
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PMID:Regulation of MPF activity in vitro. 283 64

INH, a type 2A protein phosphatase (PP2A), negatively regulates entry into M phase and the cyclin B-dependent activation of cdc2 in Xenopus extracts. INH appears to be central to the mechanism of the trigger for mitotic initiation, as it prevents the premature activation of cdc2. We first show that INH is a conventional form of PP2A with a B alpha regulatory subunit. We next explore the mechanism by which it inhibits cdc2 activation by examining the effect of purified PP2A on the reaction pathways controlling cdc2 activity. Our results suggest that although PP2A inhibits the switch in tyrosine kinase and tyrosine phosphatase activities accompanying mitosis, this switch is a consequence of the inhibition of some other rate-limiting event. In the preactivation phase, PP2A inhibits the pathway leading to T161 phosphorylation, suggesting that this activity may be one of the rate-limiting events for transition. However, our results also suggest that the accumulation of active cdc2/cyclin complexes during the lag is only one of the events required for triggering entry into mitosis.
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PMID:Inhibition of cdc2 activation by INH/PP2A. 804 24