Parallel pathways of cell cycle control during Xenopus egg activation.
Transit from M phase into interphase in many eukaryotic cells is preceded by an increase in intracellular free calcium ([Ca2+]i), which may act via calcium-dependent enzymes to trigger the M-phase/interphase transition. To test the role of the calcium- and phospholipid-dependent enzyme protein kinase C (PKC) in the M-phase/interphase transition, PKC was activated in M-phase-arrested Xenopus eggs by treatment with the phorbol ester phorbol 12-myristate 13-acetate under conditions that prevent a rise in [Ca2+]i and activation of other calcium-dependent enzymes. Under these conditions, several cellular events characteristic of transit into interphase occur: sperm chromatin decondenses, the Golgi and the nuclear envelope reassemble, and endocytosis resumes. These events are also triggered by treatment of eggs with the diacylglycerol 1,2-dioctanoyl-sn-glycerol. Surprisingly, the activity of M-phase-promoting factor (MPF), a universal regulator of M phase, remains high under these conditions. If [Ca2+]i is subsequently raised, MPF activity is rapidly destroyed. Similarly, lysates made from eggs treated with phorbol 12-myristate 13-acetate support sperm chromatin decondensation in vitro and yet retain high MPF activity, measured either as the ability to induce meiotic resumption in oocytes or as histone H1 kinase activity. These effects are not triggered by the 4 alpha-phorbol ester isomer, which does not activate PKC, and are sensitive to the PKC "pseudosubstrate" peptide. The results suggest that two, parallel signals are generated by the rise in [Ca2+]i both of which contribute to cell cycle regulation. One pathway inactivates MPF; the other pathway activates PKC.
Bement
W M
WM
Department of Zoology, Arizona State University, Tempe 85287-1501.
Capco
D G
DG
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle; D002843:Chromatin / Q000737:chemistry; D004075:Diglycerides / Q000378:metabolism; D004705:Endocytosis; D004789:Enzyme Activation; D006056:Golgi Apparatus / Q000378:metabolism; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D010063:Ovum / Q000648:ultrastructure; D011493:Protein Kinase C / Q000378:metabolism; D013379:Substrate Specificity; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014981:Xenopus
D002843:Chromatin; D004075:Diglycerides; C044295:1,2-dioctanoylglycerol; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium