A positive-feedback-based bistable 'memory module' that governs a cell fate decision.
The maturation of Xenopus oocytes can be thought of as a process of cell fate induction, with the immature oocyte representing the default fate and the mature oocyte representing the induced fate. Crucial mediators of Xenopus oocyte maturation, including the p42 mitogen-activated protein kinase (MAPK) and the cell-division cycle protein kinase Cdc2, are known to be organized into positive feedback loops. In principle, such positive feedback loops could produce an actively maintained 'memory' of a transient inductive stimulus and could explain the irreversibility of maturation. Here we show that the p42 MAPK and Cdc2 system normally generates an irreversible biochemical response from a transient stimulus, but the response becomes transient when positive feedback is blocked. Our results explain how a group of intrinsically reversible signal transducers can generate an irreversible response at a systems level, and show how a cell fate can be maintained by a self-sustaining pattern of protein kinase activation.
Xiong
Wen
W
Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, California 94305-5174, USA.
Ferrell
James E
JE
D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D025461:Feedback, Physiological; D020935:MAP Kinase Signaling System / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D008954:Models, Biological; D009865:Oocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D014982:Xenopus laevis
D011960:Receptors, Estrogen; D011374:Progesterone; D004958:Estradiol; D019908:Proto-Oncogene Proteins c-raf; D016203:CDC2 Protein Kinase; D019950:Mitogen-Activated Protein Kinase 1